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216 results on '"National Institute of Allergy and Infectious Diseases (US)"'

1. Class-wide genomic tendency throughout specific extremes in black fung

Author: European Commission, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Junta de Andalucía, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Institute of Integrative Genome Biology (US), Coleine, Claudia [0000-0002-9289-6179], Kurbessoian, Tania [0000-0003-3946-0867], Delgado-Baquerizo, Manuel [0000-0002-6499-576X], Cestaro, Alessandro [0000-0003-1439-5165], Pindo, Massimo [0000-0002-8516-9010], Armanini, Federica [0009-0007-4030-2002], Asnicar, Francesco [0000-0003-3732-1468], Isola, Daniela [0000-0002-5069-6056], Segata, Nicola [0000-0002-1583-5794], Donati, Claudio [0000-0001-8688-1651], Stajich, Jason E. [0000-0002-7591-0020], Selbmann, Laura [0000-0002-8967-3329], Coleine, Claudia, Kurbessoian, Tania, Calia, Giulia, Delgado-Baquerizo, Manuel, Cestaro, Alessandro, Pindo, Massimo, Armanini, Federica, Asnicar, Francesco, Isola, Daniela, Segata, Nicola, Donati, Claudio, Stajich, Jason E., Hoog, Sybren de, Selbmann, Laura, European Commission, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Junta de Andalucía, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Institute of Integrative Genome Biology (US), Coleine, Claudia [0000-0002-9289-6179], Kurbessoian, Tania [0000-0003-3946-0867], Delgado-Baquerizo, Manuel [0000-0002-6499-576X], Cestaro, Alessandro [0000-0003-1439-5165], Pindo, Massimo [0000-0002-8516-9010], Armanini, Federica [0009-0007-4030-2002], Asnicar, Francesco [0000-0003-3732-1468], Isola, Daniela [0000-0002-5069-6056], Segata, Nicola [0000-0002-1583-5794], Donati, Claudio [0000-0001-8688-1651], Stajich, Jason E. [0000-0002-7591-0020], Selbmann, Laura [0000-0002-8967-3329], Coleine, Claudia, Kurbessoian, Tania, Calia, Giulia, Delgado-Baquerizo, Manuel, Cestaro, Alessandro, Pindo, Massimo, Armanini, Federica, Asnicar, Francesco, Isola, Daniela, Segata, Nicola, Donati, Claudio, Stajich, Jason E., Hoog, Sybren de, and Selbmann, Laura
Abstract: The classes Dothideomycetes and Eurotiomycetes include constitutively melanized fungi adapted to extreme conditions and they are widely distributed in diverse hostile habitats worldwide. Yet, despite the growing interest in these fungi, there is a considerable gap of knowledge on their functionality. Their genomic analysis is still in its infancy and the possibility to understand their adaptive strategies and exploit their potentialities in bioremediation is very limited. Here, we supply a genome catalog of 118 black fungi, encompassing different ecologies, phylogenies and lifestyles, as a first example of a comparative genomic study at high level of diversity. Results indicate that, as a rule, Dothideomycetes show more variable genome size and that larger genomes are associated with harshest conditions; low temperature tolerance and DNA repair capacity are overrepresented in their genomes. In Eurotiomycetes high temperature tolerance and capacity to metabolize hydrocarbons are more frequently present and these abilities are positively correlated with the human presence. The genomic features are consistent with the prevalent ecologies in the two classes. Indeed, Dothideomycetes are more common in cold and dry environments with high capacity for DNA repair being consistent with the normally highly UV-impacted conditions in their habitats; in contrast, Eurotiomycetes spread mainly in hot human-impacted sites with industrial pollution. Mean annual temperature and isothermality are positively correlated with tolerance to high temperatures in Dothideomycetes, suggesting that, despite their preference for the cold, they are potentially equipped to survive even when temperatures rise due to the global warming.
Published: 2024

2. Bacterial Artificial Chromosome Reverse Genetics Approaches for SARS-CoV-2

Author: Department of Defense (US), National Institutes of Health (US), Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), San Antonio Medical Foundation, Chiem, Kevin [0000-0002-3892-5944], Nogales, Aitor [0000-0002-2424-7900], Almazán, Fernando [0000-0002-5752-8469], Ye, Chengjin [0000-0002-1934-9494], Martínez-Sobrido, Luis [0000-0001-7084-0804], Chiem, Kevin, Nogales, Aitor, Almazán, Fernando, Ye, Chengjin, Martínez-Sobrido, Luis, Department of Defense (US), National Institutes of Health (US), Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), San Antonio Medical Foundation, Chiem, Kevin [0000-0002-3892-5944], Nogales, Aitor [0000-0002-2424-7900], Almazán, Fernando [0000-0002-5752-8469], Ye, Chengjin [0000-0002-1934-9494], Martínez-Sobrido, Luis [0000-0001-7084-0804], Chiem, Kevin, Nogales, Aitor, Almazán, Fernando, Ye, Chengjin, and Martínez-Sobrido, Luis
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new member of the Coronaviridae family responsible for the coronavirus disease 19 (COVID-19) pandemic. To date, SARS-CoV-2 has been accountable for over 624 million infection cases and more than 6.5 million human deaths. The development and implementation of SARS-CoV-2 reverse genetics approaches have allowed researchers to genetically engineer infectious recombinant (r)SARS-CoV-2 to answer important questions in the biology of SARS-CoV-2 infection. Reverse genetics techniques have also facilitated the generation of rSARS-CoV-2 expressing reporter genes to expedite the identification of compounds with antiviral activity in vivo and in vitro. Likewise, reverse genetics has been used to generate attenuated forms of the virus for their potential implementation as live-attenuated vaccines (LAV) for the prevention of SARS-CoV-2 infection. Here we describe the experimental procedures for the generation of rSARS-CoV-2 using a well-established and robust bacterial artificial chromosome (BAC)-based reverse genetics system. The protocol allows to produce wild-type and mutant rSARS-CoV-2 that can be used to understand the contribution of viral proteins and/or amino acid residues in viral replication and transcription, pathogenesis and transmission, and interaction with cellular host factors.
Published: 2024

3. Concomitant administration of seasonal influenza and COVID-19 mRNA vaccines [Dataset]

Author: American Lung Association, Sociedad Andaluza de Enfermedades Infecciosas, Ministerio de Ciencia e Innovación (España), European Commission, Junta de Andalucía, National Institute of Allergy and Infectious Diseases (US), Sánchez-Céspedes, Javier [0000-0003-2707-1979], Pachón, Jerónimo [0000-0002-8166-5308], Aydillo, Teresa, Balsera-Manzanero, Maria, Rojo-Fernández, Amaya, Escalera, Alba, Salamanca-Rivera, Celia, Pachón, Jerónimo, Muñoz-García, M. M., Sánchez-Cordero, María José, Sánchez-Céspedes, Javier, García-Sastre, Adolfo, Cordero, Elisa, American Lung Association, Sociedad Andaluza de Enfermedades Infecciosas, Ministerio de Ciencia e Innovación (España), European Commission, Junta de Andalucía, National Institute of Allergy and Infectious Diseases (US), Sánchez-Céspedes, Javier [0000-0003-2707-1979], Pachón, Jerónimo [0000-0002-8166-5308], Aydillo, Teresa, Balsera-Manzanero, Maria, Rojo-Fernández, Amaya, Escalera, Alba, Salamanca-Rivera, Celia, Pachón, Jerónimo, Muñoz-García, M. M., Sánchez-Cordero, María José, Sánchez-Céspedes, Javier, García-Sastre, Adolfo, and Cordero, Elisa
Abstract: Current clinical guidelines support the concomitant administration of seasonal influenza vaccines and COVID-19 mRNA boosters vaccine. Whether dual vaccination may impact vaccine immunogenicity due to an interference between influenza or SARS-CoV-2 antigens is unknown. We aimed to understand the impact of mRNA COVID-19 vaccines administered concomitantly on the immune response to influenza vaccines. For this, 128 volunteers were vaccinated during the 22-23 influenza season. Three groups of vaccination were assembled: FLU vaccine only (46, 35%) versus volunteers that received the mRNA bivalent COVID-19 vaccines concomitantly to seasonal influenza vaccines, FluCOVID vaccine in the same arm (42, 33%) or different arm (40, 31%), respectively. Sera and whole blood were obtained the day of vaccination, +7, and +28 days after for antibody and T cells response quantification. As expected, side effects were increased in individuals who received the FluCOVID vaccine as compared to FLU vaccine only based on the known reactogenicity of mRNA vaccines. In general, antibody levels were high at 4 weeks post-vaccination and differences were found only for the H3N2 virus when administered in different arms compared to the other groups at day 28 post-vaccination. Additionally, our data showed that subjects that received the FluCOVID vaccine in different arm tended to have better antibody induction than those receiving FLU vaccines for H3N2 virus in the absence of pre-existing immunity. Furthermore, no notable differences in the influenza-specific cellular immune response were found for any of the vaccination groups. Our data supports the concomitant administration of seasonal influenza and mRNA COVID-19 vaccines.
Published: 2024

4. Concomitant administration of seasonal influenza and COVID-19 mRNA vaccines

Author: Junta de Andalucía, European Commission, National Institute of Allergy and Infectious Diseases (US), American Lung Association, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Aydillo, Teresa, Balsera-Manzanero, Maria, Rojo-Fernández, Amaya, Escalera, Alba, Salamanca-Rivera, Celia, Pachón, Jerónimo, Muñoz-García, M. M., Sánchez-Cordero, María José, Sánchez-Céspedes, Javier, García-Sastre, Adolfo, Cordero, Elisa, Junta de Andalucía, European Commission, National Institute of Allergy and Infectious Diseases (US), American Lung Association, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Aydillo, Teresa, Balsera-Manzanero, Maria, Rojo-Fernández, Amaya, Escalera, Alba, Salamanca-Rivera, Celia, Pachón, Jerónimo, Muñoz-García, M. M., Sánchez-Cordero, María José, Sánchez-Céspedes, Javier, García-Sastre, Adolfo, and Cordero, Elisa
Abstract: Current clinical guidelines support the concomitant administration of seasonal influenza vaccines and COVID-19 mRNA boosters vaccine. Whether dual vaccination may impact vaccine immunogenicity due to an interference between influenza or SARS-CoV-2 antigens is unknown. We aimed to understand the impact of mRNA COVID-19 vaccines administered concomitantly on the immune response to influenza vaccines. For this, 128 volunteers were vaccinated during the 22-23 influenza season. Three groups of vaccination were assembled: FLU vaccine only (46, 35%) versus volunteers that received the mRNA bivalent COVID-19 vaccines concomitantly to seasonal influenza vaccines, FluCOVID vaccine in the same arm (42, 33%) or different arm (40, 31%), respectively. Sera and whole blood were obtained the day of vaccination, +7, and +28 days after for antibody and T cells response quantification. As expected, side effects were increased in individuals who received the FluCOVID vaccine as compared to FLU vaccine only based on the known reactogenicity of mRNA vaccines. In general, antibody levels were high at 4 weeks post-vaccination and differences were found only for the H3N2 virus when administered in different arms compared to the other groups at day 28 post-vaccination. Additionally, our data showed that subjects that received the FluCOVID vaccine in different arm tended to have better antibody induction than those receiving FLU vaccines for H3N2 virus in the absence of pre-existing immunity. Furthermore, no notable differences in the influenza-specific cellular immune response were found for any of the vaccination groups. Our data supports the concomitant administration of seasonal influenza and mRNA COVID-19 vaccines.
Published: 2024

5. Community recommendations on cryoEM data archiving and validation

Author: Wellcome Trust, National Science Foundation (US), Department of Energy (US), National Cancer Institute (US), National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), National Institute of General Medical Sciences (US), Kleywegt, Gerard J., Adams, Paul D., Butcher, Sarah J., Lawson, Catherine L., Rohou, Alexis, Rosenthal, Peter B., Subramaniam, Sriram, Topf, Maya, Abbott, Sanja, Baldwin, Philip R., Berrisford, John M., Bricogne, Gérard, Choudhary, Preeti, Croll, Tristan I., Danev, Radostin, Ganesan, Sai J., Grant, Timothy, Gutmanas, Aleksandras, Henderson, Richard, Heymann, J. Bernard, Huiskonen, Juha T., Istrate, Andrei, Kato, Takayuki, Lander, Gabriel C., Lok, Shee-Mei, Ludtke, Steven J., Murshudov, Garib N., Pye, Ryan, Pintilie, Grigore D., Richardson, Jane S., Sachse, Carsten, Salih, Osman, Scheres, Sjors H. W., Schroeder, Gunnar F., Sorzano, Carlos Óscar S., Stagg, Scott M., Wang, Zhe, Warshamanage, Rangana, Westbrook, John D., Winn, Martyn D., Young, Jasmine Y., Burley, Stephen K., Hoch, Jeffrey C., Kurisu, Genji, Morris, Kyle, Patwardhan, Ardan, Velankar, Sameer, Wellcome Trust, National Science Foundation (US), Department of Energy (US), National Cancer Institute (US), National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), National Institute of General Medical Sciences (US), Kleywegt, Gerard J., Adams, Paul D., Butcher, Sarah J., Lawson, Catherine L., Rohou, Alexis, Rosenthal, Peter B., Subramaniam, Sriram, Topf, Maya, Abbott, Sanja, Baldwin, Philip R., Berrisford, John M., Bricogne, Gérard, Choudhary, Preeti, Croll, Tristan I., Danev, Radostin, Ganesan, Sai J., Grant, Timothy, Gutmanas, Aleksandras, Henderson, Richard, Heymann, J. Bernard, Huiskonen, Juha T., Istrate, Andrei, Kato, Takayuki, Lander, Gabriel C., Lok, Shee-Mei, Ludtke, Steven J., Murshudov, Garib N., Pye, Ryan, Pintilie, Grigore D., Richardson, Jane S., Sachse, Carsten, Salih, Osman, Scheres, Sjors H. W., Schroeder, Gunnar F., Sorzano, Carlos Óscar S., Stagg, Scott M., Wang, Zhe, Warshamanage, Rangana, Westbrook, John D., Winn, Martyn D., Young, Jasmine Y., Burley, Stephen K., Hoch, Jeffrey C., Kurisu, Genji, Morris, Kyle, Patwardhan, Ardan, and Velankar, Sameer
Abstract: In January 2020, a workshop was held at EMBL-EBI (Hinxton, UK) to discuss data requirements for the deposition and validation of cryoEM structures, with a focus on single-particle analysis. The meeting was attended by 47 experts in data processing, model building and refinement, validation, and archiving of such structures. This report describes the workshop’s motivation and history, the topics discussed, and the resulting consensus recommendations. Some challenges for future methods-development efforts in this area are also highlighted, as is the implementation to date of some of the recommendations.
Published: 2024

6. Refinement of Leishmania donovani Genome Annotations in the Light of Ribosome-Protected mRNAs Fragments (Ribo-Seq Data)

Author: Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, Fundación Ramón Areces, National Institute of Allergy and Infectious Diseases (US), Sánchez-Salvador, Alejandra, González de la Fuente, Sandra, Aguado, Begoña, Yates, Phillip A., Requena, José María, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, Fundación Ramón Areces, National Institute of Allergy and Infectious Diseases (US), Sánchez-Salvador, Alejandra, González de la Fuente, Sandra, Aguado, Begoña, Yates, Phillip A., and Requena, José María
Abstract: Advances in next-generation sequencing methodologies have facilitated the assembly of an ever-increasing number of genomes. Gene annotations are typically conducted via specialized software, but the most accurate results require additional manual curation that incorporates insights derived from functional and bioinformatic analyses (e.g., transcriptomics, proteomics, and phylogenetics). In this study, we improved the annotation of the Leishmania donovani (strain HU3) genome using publicly available data from the deep sequencing of ribosome-protected mRNA fragments (Ribo-Seq). As a result of this analysis, we uncovered 70 previously non-annotated protein-coding genes and improved the annotation of around 600 genes. Additionally, we present evidence for small upstream open reading frames (uORFs) in a significant number of transcripts, indicating their potential role in the translational regulation of gene expression. The bioinformatics pipelines developed for these analyses can be used to improve the genome annotations of other organisms for which Ribo-Seq data are available. The improvements provided by these studies will bring us closer to the ultimate goal of a complete and accurately annotated L. donovani genome and will enhance future transcriptomics, proteomics, and genetics studies.
Published: 2023

7. A comparative study of eight serological methods shows that spike protein-based ELISAs are the most accurate tests for serodiagnosing SARS-CoV-2 infections in cats and dogs

Author: Comunidad de Madrid, Universidad Complutense de Madrid, European Commission, Ministerio de Economía y Empresa (España), Universidad de Zaragoza, National Institute of Allergy and Infectious Diseases (US), Agencia Estatal de Investigación (España), Diezma-Díaz, Carlos [0000-0002-0311-1924], Álvarez-García, Gema [0000-0002-6627-7577], Regidor-Cerrillo, Javier [0000-0001-5831-6970], Miró, Guadalupe [0000-0003-0981-2470], Villanueva-Saz, Sergio [0000-0002-4874-2164], Verde, María Teresa [0000-0003-2957-1379], Galán-Malo, Patricia [0000-0003-0421-5933], Brun Torres, Alejandro [0000-0001-7865-538X], Moreno, Sandra [0000-0002-3548-037X], Checa, Rocío [0000-0003-2419-1254], Montoya, Ana [0000-0003-1911-8642], Van Voorhis, Wesley C. [0000-0001-6141-2015], Ortega-Mora, Luis Miguel [0000-0002-4986-6783], Diezma-Díaz, Carlos, Álvarez-García, Gema, Regidor-Cerrillo, Javier, Miró, Guadalupe, Villanueva-Saz, Sergio, Pérez, María Dolores, Verde, María Teresa, Galán-Malo, Patricia, Brun Torres, Alejandro, Moreno, Sandra, Checa, Rocío, Montoya, Ana, Van Voorhis, Wesley C., Ortega-Mora, Luis Miguel, Comunidad de Madrid, Universidad Complutense de Madrid, European Commission, Ministerio de Economía y Empresa (España), Universidad de Zaragoza, National Institute of Allergy and Infectious Diseases (US), Agencia Estatal de Investigación (España), Diezma-Díaz, Carlos [0000-0002-0311-1924], Álvarez-García, Gema [0000-0002-6627-7577], Regidor-Cerrillo, Javier [0000-0001-5831-6970], Miró, Guadalupe [0000-0003-0981-2470], Villanueva-Saz, Sergio [0000-0002-4874-2164], Verde, María Teresa [0000-0003-2957-1379], Galán-Malo, Patricia [0000-0003-0421-5933], Brun Torres, Alejandro [0000-0001-7865-538X], Moreno, Sandra [0000-0002-3548-037X], Checa, Rocío [0000-0003-2419-1254], Montoya, Ana [0000-0003-1911-8642], Van Voorhis, Wesley C. [0000-0001-6141-2015], Ortega-Mora, Luis Miguel [0000-0002-4986-6783], Diezma-Díaz, Carlos, Álvarez-García, Gema, Regidor-Cerrillo, Javier, Miró, Guadalupe, Villanueva-Saz, Sergio, Pérez, María Dolores, Verde, María Teresa, Galán-Malo, Patricia, Brun Torres, Alejandro, Moreno, Sandra, Checa, Rocío, Montoya, Ana, Van Voorhis, Wesley C., and Ortega-Mora, Luis Miguel
Abstract: Coronavirus disease 2019 (COVID-19) is an infectious zoonotic disease caused by SARS-CoV-2. Monitoring the infection in pets is recommended for human disease surveillance, prevention, and control since the virus can spread from people to animals during close contact. Several diagnostic tests have been adapted from humans to animals, but limited data on the validation process are available.
Published: 2023

8. Annual (2023) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota)

Author: National Institute of Allergy and Infectious Diseases (US), Antiviral Countermeasures Development Center (US), Department of Agriculture (US), Department of the Army (US), Department of Health and Human Services (US), US Department of Homeland Security, Federal Government of the United States, Kuhn, Jens H. [0000-0002-7800-6045], Abe, Junya [0000-0003-3627-7071], Adkins, Scott [0000-0003-0095-8414], Alkhovsky, Sergey V. [0000-0001-6913-5841], Avsic-Zupanc, Tatjana [0000-0001-6243-0688], Ayllón, María A. [0000-0001-7893-6106], Bahl, Justin [0000-0001-7572-4300], Balkema-Buschmann, A. [0000-0001-7613-9592], Ballinger, Matthew J. [0000-0001-7453-8725], Bejerman, Nicolas [0000-0002-7851-3506], Biedenkopf, Nadine [0000-0002-6061-8019], Blair, Carol D.[0000-0002-2803-0354], Blasdell, Kim R.[0000-0003-2121-0376], Bradfute, Steven B.[0000-0002-1985-751X], Briese, Thomas [0000-0002-4819-8963], Buchholz, Ursula J. [0000-0002-2329-3198], Buchmeier, Michael J.[0000-0002-2387-9287], Bukreyev, Alexander [0000-0002-0342-4824], Burt, Felicity [0000-0002-7238-7799], Büttner, Carmen [0000-0002-2086-2594], Calisher, Charles H. [0000-0003-0213-294X], Cao, Mengji [0000-0003-0396-262X], Casas, Inmaculada [0000-0003-1840-1198], Chandran, Kartik [0000-0003-0232-7077], Charrel, Rémi N.[0000-0002-7675-8251], Chaturvedi, Krishna Kumar [0000-0002-6529-5466], Crane, Anya [0000-0002-2060-2469], De Swart, Rik L.[0000-0003-3599-8969], Debat, Humberto [0000-0003-3056-3739], Dheilly, Nolwenn M.[0000-0002-3675-5013], Di Paola, Nicholas [0000-0002-9694-3913], Di Serio, Francesco [0000-0003-2822-704X], Dietzgen, Ralf G.[0000-0002-7772-2250], Digiaro, Michele [0009-0006-3089-3606], Drexler, J. Felix [0000-0002-3509-0232], Duprex, W. Paul [0000-0003-1716-6376], Elbeaino, Toufic [0000-0003-2211-7907], Ergünay, Koray [0000-0001-5422-1982], Feng, Guozhong [0000-0002-9489-9322], Fooks, Anthony R.[0000-0002-3243-6154], Formenty, Pierre B.H.[0000-0002-9482-5411], Freitas-Astúa, Juliana [0000-0002-0506-6880], Gago-Zachert, Selma [0000-0002-1084-2119], García, María Laura [0000-0001-6468-6943], Garrison, Aura R.[0000-0003-3034-6400], Gaskin, Thomas R. [0000-0002-5644-4431], Gouy de Bellocq, Joelle [0000-0001-5831-6284], Griffiths, Anthony [0000-0001-5435-8364], Groschup, M. H.[0000-0003-0215-185X], Günther, Stephan [0000-0002-6562-0230], Hayashi, Kazusa [0009-0002-9395-0066], Hepojoki, Jussi [0000-0001-5699-214X], Higgins, Colleen M. [0000-0001-9016-2940], Horie, Masayuki [0000-0003-4682-7698], Hughes, Holly R.[0000-0003-1380-8263], Hyndman, Timothy [0000-0002-7047-5023], Jiāng, Dàohóng [0000-0002-3862-7461], Jonson, Gilda B.[0000-0003-0097-8634], Junglen, Sandra [0000-0002-3799-6011], Klempa, B.[0000-0002-6931-1224], Klingström, Jonas [0000-0001-9076-1441], Kondō, Hideki [0000-0001-9220-5350], Koonin, Eugene V. [0000-0003-3943-8299], Krupovic, Mart [0000-0001-5486-0098], Kurath, Gael [0000-0003-3294-560X], Laenen, Lies [0000-0001-9118-8608], Li, Jianrong [0000-0002-7130-1084], Lukashevich, Igor S.[0000-0001-6523-5116], MacDiarmid, Robin M.[0000-0002-7057-2018], Maes, Piet [0000-0002-4571-5232], Marklewitz, Marco [0000-0003-1828-8770], Marshall, Sergio H.[0000-0003-0438-8252], Marzano, Shin-Yi L. [0000-0003-0548-3761], Mühlberger, Elke [0000-0003-3547-9376], Nabeshima, Tomoyuki [0000-0002-6570-096X], Naidu, Rayapati [0000-0002-7273-5116], Natsuaki, Tomohide [0000-0003-1823-7308], Navarro, José A. [0000-0002-0536-6074], Neriya, Yutaro [0000-0002-1385-0050], Netesov, Sergey V. [0000-0002-7786-2464], Neumann, Gabriele [0000-0001-7054-1775], Nowotny, N. [0000-0002-3548-571X], Ochoa-Corona, Francisco M. [0000-0002-4112-8209], Pallás, Vicente [0000-0003-4954-989X], Papa, Anna [0000-0002-6643-3322], Paraskevopoulou, Sofia [0000-0003-2608-2596], Parrish, Colin R. [0000-0002-1836-6655], Pauvolid-Corrêa, Alex [0000-0002-6924-157X], Pawęska, Janusz T. [0000-0001-8776-7519], Pérez, Daniel R. [0000-0002-6569-5689], Pfaff, Florian [0000-0003-0178-6183], Plemper, Richard K. [0000-0003-2034-2107], Postler, Thomas S. [0000-0002-3558-9084], Rabbidge, Lee O. [0009-0001-7962-4881], Radoshitzky, Sheli R. [0000-0001-8976-8056], Ramos-González, Pedro L. [0000-0002-9640-6587], Rehanek, Marius [0000-0002-5710-5060], Resende, Renato O. [0000-0003-3852-1576], Romanowski, Víctor [0000-0001-6378-7929], Rubbenstroth, Dennis [0000-0002-8209-6274], Rubino, Luisa [0000-0002-2073-2415], Runstadler, Jonathan A. [0000-0002-6747-7765], Sabanadzovic, Sead [0000-0002-2995-2633], Salvato, Maria S. [0000-0002-3357-5391], Sasaya, Takahide [0000-0002-5020-9377], Schwemmle, Martin [0000-0002-2972-6855], Shi, Mang [0000-0002-6154-4437], Shimomoto, Yoshifumi [0000-0002-0796-7068], Kavi Sidharthan, Venkidusamy [0000-0003-1561-549X], Sironi, Manuela [0000-0002-2267-5266], Smither, Sophie [0000-0002-7835-3581], Spann, Kirsten [0000-0003-0567-8382], Spengler, Jessica R. [0000-0002-5383-0513], Stenglein, Mark D. [0000-0002-0993-813X], Takada, Ayato [0000-0003-2464-6642], Takeyama, Sawana [0009-0000-3771-5999], Tesh, Robert B. [0000-0002-9226-397X], Thornburg, Natalie J. [0000-0003-3523-3616], Tischler, Nicole D. [0000-0002-4578-4780], Tomitaka, Yasuhiro [0000-0002-6914-4016], Tomonaga, Keizō [0000-0003-0405-7103], Tordo, Noël [0000-0001-5873-059X], Tu, Changchun [0000-0002-8134-7502], Turina, Massimo [0000-0002-9659-9470], Tzanetakis, Ioannis E. [0000-0002-5970-1763], Vaira, Anna Maria [0000-0003-2526-4419], Van den Hoogen, Bernadette [0000-0003-1996-8559], Vanmechelen, Bert [0000-0002-8350-4356], Verbeek, Martin [0000-0002-8973-3803], Von Bargen, Susanne [0000-0001-8321-1572], Wada, Jiro [0000-0001-9846-0846], Wahl, Victoria [0000-0002-6588-4308], Walker, Peter J. [0000-0003-1851-642X], Waltzek, Thomas B. [0000-0001-6383-5978], Whitfield, Anna E. [0000-0002-3538-015X], Wolf, Yuri I. [0000-0002-0247-8708], Xylogianni, Evanthia [0009-0001-8768-0939], Yanagisawa, Hironobu [0000-0002-6729-466X], Ye, Gongyin [0000-0003-4937-8867], Yuan, Zhiming [0000-0002-3234-9616], Zerbini, F. Murilo [0000-0001-8617-0200], Okland, Arnfinn Lodden [0000-0003-3062-4386], Kuhn, Jens H., Abe, Junya, Adkins, Scott, Alkhovsky, Sergey V., Avsic-Zupanc, Tatjana, Ayllón, María A., Bahl, Justin, Balkema-Buschmann, A., Ballinger, Matthew J., Kumar Baranwal, Virendra, Beer, Martin, Bejerman, Nicolas, Bergeron, Éric, Biedenkopf, Nadine, Blair, Carol D., Blasdell, Kim R., Blouin, Arnaud G., Bradfute, Steven B., Briese, Thomas, Brown, Paul A., Buchholz, Ursula J., Buchmeier, Michael J., Bukreyev, Alexander, Burt, Felicity, Büttner, Carmen, Calisher, Charles H., Cao, Mengji, Casas, Inmaculada, Chandran, Kartik, Charrel, Rémi N., Chaturvedi, Krishna Kumar, Chooi, Kar Mun, Crane, Anya, Dal Bó, Elena, de la Torre, J. C., de Souza, William Marciel, De Swart, Rik L., Debat, Humberto, Dheilly, Nolwenn M., Di Paola, Nicholas, Di Serio, Francesco, Dietzgen, Ralf G., Digiaro, Michele, Drexler, J. Felix, Duprex, W. Paul, Dürrwald, Ralf, Easton, Andrew J., Elbeaino, Toufic, Ergünay, Koray, Feng, Guozhong, Firth, Andrew E., Fooks, Anthony R., Formenty, Pierre B.H., Freitas-Astúa, Juliana, Gago-Zachert, Selma, García, María Laura, García-Sastre, Adolfo, Garrison, Aura R., Gaskin, Thomas R., Gong, Wenjie, Gonzalez, Jean-Paul J., Gouy de Bellocq, Joelle, Griffiths, Anthony, Groschup, M. H., Günther, Ines, Günther, Stephan, Hammond, John, Hasegawa, Yusuke, Hayashi, Kazusa, Hepojoki, Jussi, Higgins, Colleen M., Hongo, Seiji, Horie, Masayuki, Hughes, Holly R., Hume, Adam J., Hyndman, Timothy, Ikeda, Kenichi, Jiāng, Dàohóng, Jonson, Gilda B., Junglen, Sandra, Klempa, B., Klingström, Jonas, Kondō, Hideki, Koonin, Eugene V., Krupovic, Mart, Kubota, Kenji, Kurath, Gael, Laenen, Lies, Lambert, Amy J., Li, Jianrong, Li, Jun-Min, Liu, Ran, Lukashevich, Igor S., MacDiarmid, Robin M, Maes, Piet, Marklewitz, Marco, Marshall, Sergio H., Marzano, Shin-Yi L., McCauley, John W., Mirazimi, Ali, Mühlberger, Elke, Nabeshima, Tomoyuki, Naidu, Rayapati, Natsuaki, Tomohide, Navarro, Beatriz, Navarro, José A., Neriya, Yutaro, Netesov, Sergey V., Neumann, Gabriele, Nowotny, N., Nunes, Márcio R.T., Ochoa-Corona, Francisco M., Okada, Tomoyuki, Palacios, Gustavo, Pallás, Vicente, Papa, Anna, Paraskevopoulou, Sofia, Parrish, Colin R., Pauvolid-Corrêa, Alex, Pawęska, Janusz T., Pérez, Daniel R., Pfaff, Florian, Plemper, Richard K., Postler, Thomas S., Rabbidge, Lee O., Radoshitzky, Sheli R., Ramos-González, Pedro L., Rehanek, Marius, Resende, Renato O., Reyes, Carina A., Rodrigues, Thaís C.S., Romanowski, Víctor, Rubbenstroth, Dennis, Rubino, Luisa, Runstadler, Jonathan A., Sabanadzovic, Sead, Sadiq, Sabrina, Salvato, Maria S., Sasaya, Takahide, Schwemmle, Martin, Sharpe, Stephen R., Shi, Mang, Shimomoto, Yoshifumi, Kavi Sidharthan, Venkidusamy, Sironi, Manuela, Smither, Sophie, Song, Jin-Won, Spann, Kirsten, Spengler, Jessica R., Stenglein, Mark D., Takada, Ayato, Takeyama, Sawana, Tatara, Akio, Tesh, Robert B., Thornburg, Natalie J., Tian, Xin, Tischler, Nicole D., Tomitaka, Yasuhiro, Tomonaga, Keizō, Tordo, Noël, Tu, Changchun, Turina, Massimo, Tzanetakis, Ioannis E., Vaira, Anna Maria, Van den Hoogen, Bernadette, Vanmechelen, Bert, Vasilakis, Nikos, Verbeek, Martin, Von Bargen, Susanne, Wada, Jiro, Wahl, Victoria, Walker, Peter J., Waltzek, Thomas B., Whitfield, Anna E., Wolf, Yuri I., Xia, Han, Xylogianni, Evanthia, Yanagisawa, Hironobu, Yano, Kazutaka, Ye, Gongyin, Yuan, Zhiming, Zerbini, F. Murilo, Zhang, Guilin, Zhang, Song, Zhang, Yong-Zhen, Zhao, Lu, Okland, Arnfinn Lodden, National Institute of Allergy and Infectious Diseases (US), Antiviral Countermeasures Development Center (US), Department of Agriculture (US), Department of the Army (US), Department of Health and Human Services (US), US Department of Homeland Security, Federal Government of the United States, Kuhn, Jens H. [0000-0002-7800-6045], Abe, Junya [0000-0003-3627-7071], Adkins, Scott [0000-0003-0095-8414], Alkhovsky, Sergey V. [0000-0001-6913-5841], Avsic-Zupanc, Tatjana [0000-0001-6243-0688], Ayllón, María A. [0000-0001-7893-6106], Bahl, Justin [0000-0001-7572-4300], Balkema-Buschmann, A. [0000-0001-7613-9592], Ballinger, Matthew J. [0000-0001-7453-8725], Bejerman, Nicolas [0000-0002-7851-3506], Biedenkopf, Nadine [0000-0002-6061-8019], Blair, Carol D.[0000-0002-2803-0354], Blasdell, Kim R.[0000-0003-2121-0376], Bradfute, Steven B.[0000-0002-1985-751X], Briese, Thomas [0000-0002-4819-8963], Buchholz, Ursula J. [0000-0002-2329-3198], Buchmeier, Michael J.[0000-0002-2387-9287], Bukreyev, Alexander [0000-0002-0342-4824], Burt, Felicity [0000-0002-7238-7799], Büttner, Carmen [0000-0002-2086-2594], Calisher, Charles H. [0000-0003-0213-294X], Cao, Mengji [0000-0003-0396-262X], Casas, Inmaculada [0000-0003-1840-1198], Chandran, Kartik [0000-0003-0232-7077], Charrel, Rémi N.[0000-0002-7675-8251], Chaturvedi, Krishna Kumar [0000-0002-6529-5466], Crane, Anya [0000-0002-2060-2469], De Swart, Rik L.[0000-0003-3599-8969], Debat, Humberto [0000-0003-3056-3739], Dheilly, Nolwenn M.[0000-0002-3675-5013], Di Paola, Nicholas [0000-0002-9694-3913], Di Serio, Francesco [0000-0003-2822-704X], Dietzgen, Ralf G.[0000-0002-7772-2250], Digiaro, Michele [0009-0006-3089-3606], Drexler, J. Felix [0000-0002-3509-0232], Duprex, W. Paul [0000-0003-1716-6376], Elbeaino, Toufic [0000-0003-2211-7907], Ergünay, Koray [0000-0001-5422-1982], Feng, Guozhong [0000-0002-9489-9322], Fooks, Anthony R.[0000-0002-3243-6154], Formenty, Pierre B.H.[0000-0002-9482-5411], Freitas-Astúa, Juliana [0000-0002-0506-6880], Gago-Zachert, Selma [0000-0002-1084-2119], García, María Laura [0000-0001-6468-6943], Garrison, Aura R.[0000-0003-3034-6400], Gaskin, Thomas R. [0000-0002-5644-4431], Gouy de Bellocq, Joelle [0000-0001-5831-6284], Griffiths, Anthony [0000-0001-5435-8364], Groschup, M. H.[0000-0003-0215-185X], Günther, Stephan [0000-0002-6562-0230], Hayashi, Kazusa [0009-0002-9395-0066], Hepojoki, Jussi [0000-0001-5699-214X], Higgins, Colleen M. [0000-0001-9016-2940], Horie, Masayuki [0000-0003-4682-7698], Hughes, Holly R.[0000-0003-1380-8263], Hyndman, Timothy [0000-0002-7047-5023], Jiāng, Dàohóng [0000-0002-3862-7461], Jonson, Gilda B.[0000-0003-0097-8634], Junglen, Sandra [0000-0002-3799-6011], Klempa, B.[0000-0002-6931-1224], Klingström, Jonas [0000-0001-9076-1441], Kondō, Hideki [0000-0001-9220-5350], Koonin, Eugene V. [0000-0003-3943-8299], Krupovic, Mart [0000-0001-5486-0098], Kurath, Gael [0000-0003-3294-560X], Laenen, Lies [0000-0001-9118-8608], Li, Jianrong [0000-0002-7130-1084], Lukashevich, Igor S.[0000-0001-6523-5116], MacDiarmid, Robin M.[0000-0002-7057-2018], Maes, Piet [0000-0002-4571-5232], Marklewitz, Marco [0000-0003-1828-8770], Marshall, Sergio H.[0000-0003-0438-8252], Marzano, Shin-Yi L. [0000-0003-0548-3761], Mühlberger, Elke [0000-0003-3547-9376], Nabeshima, Tomoyuki [0000-0002-6570-096X], Naidu, Rayapati [0000-0002-7273-5116], Natsuaki, Tomohide [0000-0003-1823-7308], Navarro, José A. [0000-0002-0536-6074], Neriya, Yutaro [0000-0002-1385-0050], Netesov, Sergey V. [0000-0002-7786-2464], Neumann, Gabriele [0000-0001-7054-1775], Nowotny, N. [0000-0002-3548-571X], Ochoa-Corona, Francisco M. [0000-0002-4112-8209], Pallás, Vicente [0000-0003-4954-989X], Papa, Anna [0000-0002-6643-3322], Paraskevopoulou, Sofia [0000-0003-2608-2596], Parrish, Colin R. [0000-0002-1836-6655], Pauvolid-Corrêa, Alex [0000-0002-6924-157X], Pawęska, Janusz T. [0000-0001-8776-7519], Pérez, Daniel R. [0000-0002-6569-5689], Pfaff, Florian [0000-0003-0178-6183], Plemper, Richard K. [0000-0003-2034-2107], Postler, Thomas S. [0000-0002-3558-9084], Rabbidge, Lee O. [0009-0001-7962-4881], Radoshitzky, Sheli R. [0000-0001-8976-8056], Ramos-González, Pedro L. [0000-0002-9640-6587], Rehanek, Marius [0000-0002-5710-5060], Resende, Renato O. [0000-0003-3852-1576], Romanowski, Víctor [0000-0001-6378-7929], Rubbenstroth, Dennis [0000-0002-8209-6274], Rubino, Luisa [0000-0002-2073-2415], Runstadler, Jonathan A. [0000-0002-6747-7765], Sabanadzovic, Sead [0000-0002-2995-2633], Salvato, Maria S. [0000-0002-3357-5391], Sasaya, Takahide [0000-0002-5020-9377], Schwemmle, Martin [0000-0002-2972-6855], Shi, Mang [0000-0002-6154-4437], Shimomoto, Yoshifumi [0000-0002-0796-7068], Kavi Sidharthan, Venkidusamy [0000-0003-1561-549X], Sironi, Manuela [0000-0002-2267-5266], Smither, Sophie [0000-0002-7835-3581], Spann, Kirsten [0000-0003-0567-8382], Spengler, Jessica R. [0000-0002-5383-0513], Stenglein, Mark D. [0000-0002-0993-813X], Takada, Ayato [0000-0003-2464-6642], Takeyama, Sawana [0009-0000-3771-5999], Tesh, Robert B. [0000-0002-9226-397X], Thornburg, Natalie J. [0000-0003-3523-3616], Tischler, Nicole D. [0000-0002-4578-4780], Tomitaka, Yasuhiro [0000-0002-6914-4016], Tomonaga, Keizō [0000-0003-0405-7103], Tordo, Noël [0000-0001-5873-059X], Tu, Changchun [0000-0002-8134-7502], Turina, Massimo [0000-0002-9659-9470], Tzanetakis, Ioannis E. [0000-0002-5970-1763], Vaira, Anna Maria [0000-0003-2526-4419], Van den Hoogen, Bernadette [0000-0003-1996-8559], Vanmechelen, Bert [0000-0002-8350-4356], Verbeek, Martin [0000-0002-8973-3803], Von Bargen, Susanne [0000-0001-8321-1572], Wada, Jiro [0000-0001-9846-0846], Wahl, Victoria [0000-0002-6588-4308], Walker, Peter J. [0000-0003-1851-642X], Waltzek, Thomas B. [0000-0001-6383-5978], Whitfield, Anna E. [0000-0002-3538-015X], Wolf, Yuri I. [0000-0002-0247-8708], Xylogianni, Evanthia [0009-0001-8768-0939], Yanagisawa, Hironobu [0000-0002-6729-466X], Ye, Gongyin [0000-0003-4937-8867], Yuan, Zhiming [0000-0002-3234-9616], Zerbini, F. Murilo [0000-0001-8617-0200], Okland, Arnfinn Lodden [0000-0003-3062-4386], Kuhn, Jens H., Abe, Junya, Adkins, Scott, Alkhovsky, Sergey V., Avsic-Zupanc, Tatjana, Ayllón, María A., Bahl, Justin, Balkema-Buschmann, A., Ballinger, Matthew J., Kumar Baranwal, Virendra, Beer, Martin, Bejerman, Nicolas, Bergeron, Éric, Biedenkopf, Nadine, Blair, Carol D., Blasdell, Kim R., Blouin, Arnaud G., Bradfute, Steven B., Briese, Thomas, Brown, Paul A., Buchholz, Ursula J., Buchmeier, Michael J., Bukreyev, Alexander, Burt, Felicity, Büttner, Carmen, Calisher, Charles H., Cao, Mengji, Casas, Inmaculada, Chandran, Kartik, Charrel, Rémi N., Chaturvedi, Krishna Kumar, Chooi, Kar Mun, Crane, Anya, Dal Bó, Elena, de la Torre, J. C., de Souza, William Marciel, De Swart, Rik L., Debat, Humberto, Dheilly, Nolwenn M., Di Paola, Nicholas, Di Serio, Francesco, Dietzgen, Ralf G., Digiaro, Michele, Drexler, J. Felix, Duprex, W. Paul, Dürrwald, Ralf, Easton, Andrew J., Elbeaino, Toufic, Ergünay, Koray, Feng, Guozhong, Firth, Andrew E., Fooks, Anthony R., Formenty, Pierre B.H., Freitas-Astúa, Juliana, Gago-Zachert, Selma, García, María Laura, García-Sastre, Adolfo, Garrison, Aura R., Gaskin, Thomas R., Gong, Wenjie, Gonzalez, Jean-Paul J., Gouy de Bellocq, Joelle, Griffiths, Anthony, Groschup, M. H., Günther, Ines, Günther, Stephan, Hammond, John, Hasegawa, Yusuke, Hayashi, Kazusa, Hepojoki, Jussi, Higgins, Colleen M., Hongo, Seiji, Horie, Masayuki, Hughes, Holly R., Hume, Adam J., Hyndman, Timothy, Ikeda, Kenichi, Jiāng, Dàohóng, Jonson, Gilda B., Junglen, Sandra, Klempa, B., Klingström, Jonas, Kondō, Hideki, Koonin, Eugene V., Krupovic, Mart, Kubota, Kenji, Kurath, Gael, Laenen, Lies, Lambert, Amy J., Li, Jianrong, Li, Jun-Min, Liu, Ran, Lukashevich, Igor S., MacDiarmid, Robin M, Maes, Piet, Marklewitz, Marco, Marshall, Sergio H., Marzano, Shin-Yi L., McCauley, John W., Mirazimi, Ali, Mühlberger, Elke, Nabeshima, Tomoyuki, Naidu, Rayapati, Natsuaki, Tomohide, Navarro, Beatriz, Navarro, José A., Neriya, Yutaro, Netesov, Sergey V., Neumann, Gabriele, Nowotny, N., Nunes, Márcio R.T., Ochoa-Corona, Francisco M., Okada, Tomoyuki, Palacios, Gustavo, Pallás, Vicente, Papa, Anna, Paraskevopoulou, Sofia, Parrish, Colin R., Pauvolid-Corrêa, Alex, Pawęska, Janusz T., Pérez, Daniel R., Pfaff, Florian, Plemper, Richard K., Postler, Thomas S., Rabbidge, Lee O., Radoshitzky, Sheli R., Ramos-González, Pedro L., Rehanek, Marius, Resende, Renato O., Reyes, Carina A., Rodrigues, Thaís C.S., Romanowski, Víctor, Rubbenstroth, Dennis, Rubino, Luisa, Runstadler, Jonathan A., Sabanadzovic, Sead, Sadiq, Sabrina, Salvato, Maria S., Sasaya, Takahide, Schwemmle, Martin, Sharpe, Stephen R., Shi, Mang, Shimomoto, Yoshifumi, Kavi Sidharthan, Venkidusamy, Sironi, Manuela, Smither, Sophie, Song, Jin-Won, Spann, Kirsten, Spengler, Jessica R., Stenglein, Mark D., Takada, Ayato, Takeyama, Sawana, Tatara, Akio, Tesh, Robert B., Thornburg, Natalie J., Tian, Xin, Tischler, Nicole D., Tomitaka, Yasuhiro, Tomonaga, Keizō, Tordo, Noël, Tu, Changchun, Turina, Massimo, Tzanetakis, Ioannis E., Vaira, Anna Maria, Van den Hoogen, Bernadette, Vanmechelen, Bert, Vasilakis, Nikos, Verbeek, Martin, Von Bargen, Susanne, Wada, Jiro, Wahl, Victoria, Walker, Peter J., Waltzek, Thomas B., Whitfield, Anna E., Wolf, Yuri I., Xia, Han, Xylogianni, Evanthia, Yanagisawa, Hironobu, Yano, Kazutaka, Ye, Gongyin, Yuan, Zhiming, Zerbini, F. Murilo, Zhang, Guilin, Zhang, Song, Zhang, Yong-Zhen, Zhao, Lu, and Okland, Arnfinn Lodden
Abstract: In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
Published: 2023

9. Identification of In Vitro Inhibitors of Monkeypox Replication

Author: Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Antiviral Countermeasures Development Center (US), National Institutes of Health (US), Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), San Antonio Medical Foundation, Texas Biomedical Forum, Chiem, Kevin [0000-0002-3892-5944], Nogales, Aitor [0000-0002-2424-7900], Lorenzo, María M. [0000-0001-7588-673X], Morales Vasquez, Desarey [0000-0002-7357-9821], Xiang, Yan [0000-0002-7633-1629], Gupta, Yogesh Kumar [0000-0002-9438-6279], Blasco, Rafael [0000-0002-8819-5767], de la Torre, J. C. [0000-0002-8171-8115], Martínez-Sobrido, Luis [0000-0001-7084-0804], Chiem, Kevin, Nogales, Aitor, Lorenzo, María M., Morales Vasquez, Desarey, Xiang, Yan, Gupta, Yogesh Kumar, Blasco, Rafael, de la Torre, J. C., Martínez-Sobrido, Luis, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Antiviral Countermeasures Development Center (US), National Institutes of Health (US), Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), San Antonio Medical Foundation, Texas Biomedical Forum, Chiem, Kevin [0000-0002-3892-5944], Nogales, Aitor [0000-0002-2424-7900], Lorenzo, María M. [0000-0001-7588-673X], Morales Vasquez, Desarey [0000-0002-7357-9821], Xiang, Yan [0000-0002-7633-1629], Gupta, Yogesh Kumar [0000-0002-9438-6279], Blasco, Rafael [0000-0002-8819-5767], de la Torre, J. C. [0000-0002-8171-8115], Martínez-Sobrido, Luis [0000-0001-7084-0804], Chiem, Kevin, Nogales, Aitor, Lorenzo, María M., Morales Vasquez, Desarey, Xiang, Yan, Gupta, Yogesh Kumar, Blasco, Rafael, de la Torre, J. C., and Martínez-Sobrido, Luis
Abstract: Monkeypox virus (MPXV) infections in humans have historically been restricted to regions of endemicity in Africa. However, in 2022, an alarming number of MPXV cases were reported globally, with evidence of person-to-person transmission. Because of this, the World Health Organization (WHO) declared the MPXV outbreak a public health emergency of international concern. The supply of MPXV vaccines is limited, and only two antivirals, tecovirimat and brincidofovir, approved by the U.S. Food and Drug Administration (FDA) for the treatment of smallpox, are currently available for the treatment of MPXV infection. Here, we evaluated 19 compounds previously shown to inhibit different RNA viruses for their ability to inhibit orthopoxvirus infections. We first used recombinant vaccinia virus (rVACV) expressing fluorescence (mScarlet or green fluorescent protein [GFP]) and luciferase (Nluc) reporter genes to identify compounds with antiorthopoxvirus activity. Seven compounds from the ReFRAME library (antimycin A, mycophenolic acid, AVN-944, pyrazofurin, mycophenolate mofetil, azaribine, and brequinar) and six compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) showed inhibitory activity against rVACV. Notably, the anti-VACV activity of some of the compounds in the ReFRAME library (antimycin A, mycophenolic acid, AVN-944, mycophenolate mofetil, and brequinar) and all the compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) were confirmed with MPXV, demonstrating their inhibitory activity in vitro against two orthopoxviruses. IMPORTANCE Despite the eradication of smallpox, some orthopoxviruses remain important human pathogens, as exemplified by the recent 2022 monkeypox virus (MPXV) outbreak. Although smallpox vaccines are effective against MPXV, access to those vaccines is limited. In addition, current antiviral treatment against MPXV infections is limited to the use of the FDA
Published: 2023

10. Untargeted serum metabolomic analysis reveals a role for purinergic signaling in FPIES

Author: Louis and Rachel Rudin Foundation, National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Genentech, Astellas Pharma, Novartis, Lozano-Ojalvo, Daniel, Chen, Xin, Dunkin, David, Agashe, Charuta, Baker, Mary Grace, Bird, J. Andrew, Molina, Elena, Nowak-Wegrzyn, A., Berin, M. Cecilia, Louis and Rachel Rudin Foundation, National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Genentech, Astellas Pharma, Novartis, Lozano-Ojalvo, Daniel, Chen, Xin, Dunkin, David, Agashe, Charuta, Baker, Mary Grace, Bird, J. Andrew, Molina, Elena, Nowak-Wegrzyn, A., and Berin, M. Cecilia
Abstract: [Background]: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with a typical onset in infancy. Its symptoms are distinct from those of IgE-mediated food allergies and include severe repetitive vomiting, lethargy, and pallor. FPIES reactions are associated with TH17 cytokines and a systemic innate immune activation; however, the link between immune activation and symptoms is poorly understood., [Objective]: Our aim was to use an untargeted metabolomics approach to identify novel pathways associated with FPIES reactions., [Methods]: Serum samples were obtained before, during, and after oral food challenge (OFC) (10 subjects with FPIES and 10 asymptomatic subjects), and they were analyzed by untargeted metabolomics. Two-way ANOVA with false discovery rate adjustment was used for analysis of metabolites. Stomach and duodenal biopsy specimens from non-FPIES donors were stimulated with adenosine in vitro and serotonin measured by immunoassay., [Results]: The levels of a total of 34 metabolites, including inosine and urate of the purine signaling pathway, were increased during OFCs performed on the patients with symptomatic FPIES compared with the levels found for asymptomatic subjects. Expression of the purine receptors P2RX7 and P2RY10 and the ectonucleotidase CD73 in peripheral blood was significantly reduced after OFC of the patients with FPIES. The level of the serotonin metabolite 5-hydroxyindoleacetate was significantly elevated after reaction. Adenosine stimulation of gastric and duodenal biopsy specimens from FPIES-free donors induced a significant release of serotonin, suggesting a link between purinergic pathway activation and serotonin release., [Conclusions]: Activation of the purinergic pathway during FPIES reactions provides a possible mechanism connecting inflammation and vomiting by triggering serotonin release from gastric and duodenal mucosa.
Published: 2023

11. The impact of dupilumab treatment on SARS-CoV-2 T cell responses in atopic dermatitis patients

Author: Icahn School of Medicine at Mount Sinai, Sanofi, Sanofi España, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Ungar, Benjamin, Hartzell, Susan, Lozano-Ojalvo, Daniel, Ghalili, Sabrina, Bose, Swaroop, Golant, Alexandra K., Tan, Kathryn, Estrada, Yeriel D., Singer, Giselle K., Pavel, Ana B., Cravedi, Paolo, Guttman-Yassky, Emma, Icahn School of Medicine at Mount Sinai, Sanofi, Sanofi España, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Ungar, Benjamin, Hartzell, Susan, Lozano-Ojalvo, Daniel, Ghalili, Sabrina, Bose, Swaroop, Golant, Alexandra K., Tan, Kathryn, Estrada, Yeriel D., Singer, Giselle K., Pavel, Ana B., Cravedi, Paolo, and Guttman-Yassky, Emma
Published: 2023

12. MAVS Positively Regulates Mitochondrial Integrity and Metabolic Fitness in B Cells

Author: National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), National Heart, Lung, and Blood Institute (US), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Wang, Hongsheng, Sun, Wenxiang, Traba, Javier, Wu, Juan, Qi, Chen-Feng, Amo, Laura, Kole, Hemanta K., Scott, Bethany, Singh, Komudi, Sack, Michael N., Bolland, Silvia, National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), National Heart, Lung, and Blood Institute (US), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Wang, Hongsheng, Sun, Wenxiang, Traba, Javier, Wu, Juan, Qi, Chen-Feng, Amo, Laura, Kole, Hemanta K., Scott, Bethany, Singh, Komudi, Sack, Michael N., and Bolland, Silvia
Abstract: Activated B cells experience metabolic changes that require mitochondrial remodeling, in a process incompletely defined. In this study, we report that mitochondrial antiviral signaling protein (MAVS) is involved in BCR-initiated cellular proliferation and prolonged survival. MAVS is well known as a mitochondrial-tethered signaling adaptor with a central role in viral RNA-sensing pathways that induce type I IFN. The role of MAVS downstream of BCR stimulation was recognized in absence of IFN, indicative of a path for MAVS activation that is independent of viral infection. Mitochondria of BCR-activated MAVS-deficient mouse B cells exhibited a damaged phenotype including disrupted mitochondrial morphology, excess mitophagy, and the temporal progressive blunting of mitochondrial oxidative capacity with mitochondrial hyperpolarization and cell death. Costimulation of MAVS-deficient B cells with anti-CD40, in addition to BCR stimulation, partially corrected the mitochondrial structural defects and functionality. Our data reveal a (to our knowledge) previously unrecognized role of MAVS in controlling the metabolic fitness of B cells, most noticeable in the absence of costimulatory help. ImmunoHorizons, 2023, 7: 587–599.
Published: 2023

13. Mechanisms by which the cystic fibrosis transmembrane conductance regulator may influence SARS-CoV-2 infection and COVID-19 disease severity

Author: Ministero della Salute, Istituti di Ricovero e Cura a Carattere Scientifico, European Commission, Research Council of Norway, Federal Ministry of Education and Research (Germany), Banca Intesa Sanpaolo, Institut Germans Trias i Pujol, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Agència de Gestió d'Ajuts Universitaris i de Recerca, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Tedbury, Philip R., Manfredi, Candela, Degenhardt, Frauke, Conway, Joseph, Horwath, Michael C., McCracken, Courtney, Sorscher, Adam J., Moreau, Sandy, Wright, Christine, Edwards, Carolina, Brewer, Jo, Guarner, Jeannette, Wit, Emmie de, Williamson, Brandi N., Suthar, Mehul S., Ong, Yee T., Roback, John D., Alter, David N., Holter, Jan C., Karlsen, Tom H., Sacchi, Nicoletta, Romero-Gómez, Manuel, Invernizzi, Pietro, Fernández, Javier, Buti, Maria, Albillos, Agustin, Julià, Antonio, Valenti, Luca, Asselta, Rosanna, Banales, Jesús M., Bujanda, Luis, Cid, Rafael de, Franke, André, Severe COVID-19 GWAS group, Horra, Carmen de la, Maya-Miles, Douglas, Calderón, Enrique J., Medrano, Francisco Javier, Ampuero, Javier, Martín, Javier, Dopazo, Joaquín, Delgado, Juan, Guerrero, Juan M., Acosta-Herrera, Marialbert, Gallego-Durán, Rocío, Morilla Romero de la Osa, R., Friaza Patiño, Vicente, Sarafianos, Stefan G., Hong, Jeong S., Sorscher, Eric J., Ehrhardt, Annette, Ministero della Salute, Istituti di Ricovero e Cura a Carattere Scientifico, European Commission, Research Council of Norway, Federal Ministry of Education and Research (Germany), Banca Intesa Sanpaolo, Institut Germans Trias i Pujol, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Agència de Gestió d'Ajuts Universitaris i de Recerca, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Tedbury, Philip R., Manfredi, Candela, Degenhardt, Frauke, Conway, Joseph, Horwath, Michael C., McCracken, Courtney, Sorscher, Adam J., Moreau, Sandy, Wright, Christine, Edwards, Carolina, Brewer, Jo, Guarner, Jeannette, Wit, Emmie de, Williamson, Brandi N., Suthar, Mehul S., Ong, Yee T., Roback, John D., Alter, David N., Holter, Jan C., Karlsen, Tom H., Sacchi, Nicoletta, Romero-Gómez, Manuel, Invernizzi, Pietro, Fernández, Javier, Buti, Maria, Albillos, Agustin, Julià, Antonio, Valenti, Luca, Asselta, Rosanna, Banales, Jesús M., Bujanda, Luis, Cid, Rafael de, Franke, André, Severe COVID-19 GWAS group, Horra, Carmen de la, Maya-Miles, Douglas, Calderón, Enrique J., Medrano, Francisco Javier, Ampuero, Javier, Martín, Javier, Dopazo, Joaquín, Delgado, Juan, Guerrero, Juan M., Acosta-Herrera, Marialbert, Gallego-Durán, Rocío, Morilla Romero de la Osa, R., Friaza Patiño, Vicente, Sarafianos, Stefan G., Hong, Jeong S., Sorscher, Eric J., and Ehrhardt, Annette
Abstract: Patients with cystic fibrosis (CF) exhibit pronounced respiratory damage and were initially considered among those at highest risk for serious harm from SARS-CoV-2 infection. Numerous clinical studies have subsequently reported that individuals with CF in North America and Europe—while susceptible to severe COVID-19—are often spared from the highest levels of virus-associated mortality. To understand features that might influence COVID-19 among patients with cystic fibrosis, we studied relationships between SARS-CoV-2 and the gene responsible for CF (i.e., the cystic fibrosis transmembrane conductance regulator, CFTR). In contrast to previous reports, we found no association between CFTR carrier status (mutation heterozygosity) and more severe COVID-19 clinical outcomes. We did observe an unexpected trend toward higher mortality among control individuals compared with silent carriers of the common F508del CFTR variant—a finding that will require further study. We next performed experiments to test the influence of homozygous CFTR deficiency on viral propagation and showed that SARS-CoV-2 production in primary airway cells was not altered by the absence of functional CFTR using two independent protocols. On the contrary, experiments performed in vitro strongly indicated that virus proliferation depended on features of the mucosal fluid layer known to be disrupted by absent CFTR in patients with CF, including both low pH and increased viscosity. These results point to the acidic, viscous, and mucus-obstructed airways in patients with cystic fibrosis as unfavorable for the establishment of coronaviral infection. Our findings provide new and important information concerning relationships between the CF clinical phenotype and severity of COVID-19.
Published: 2023

14. Rapid, efficient auxin-inducible protein degradation in Candida pathogens

Author: National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), National Center for Advancing Translational Sciences (US), Purdue University, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Consejo Superior de Investigaciones Científicas (España), European Commission, Junta de Castilla y León, Briggs, Scott D. [0000-0003-2852-3594], Hall, Mark C. [0000-0001-6429-2506], Milholland, Kedric L., Gregor, Justin B., Hoda, Smriti, Píriz-Antúnez, Soledad, Dueñas-Santero, Encarnación, Vu, Bao Gia, Patel, Krishna P., Moye-Rowley, W. Scott, Vázquez de Aldana, Carlos R., Correa-Bordes, Jaime, Briggs, Scott D., Hall, Mark C., National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), National Center for Advancing Translational Sciences (US), Purdue University, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Consejo Superior de Investigaciones Científicas (España), European Commission, Junta de Castilla y León, Briggs, Scott D. [0000-0003-2852-3594], Hall, Mark C. [0000-0001-6429-2506], Milholland, Kedric L., Gregor, Justin B., Hoda, Smriti, Píriz-Antúnez, Soledad, Dueñas-Santero, Encarnación, Vu, Bao Gia, Patel, Krishna P., Moye-Rowley, W. Scott, Vázquez de Aldana, Carlos R., Correa-Bordes, Jaime, Briggs, Scott D., and Hall, Mark C.
Abstract: A variety of inducible protein degradation (IPD) systems have been developed as powerful tools for protein functional characterization. IPD systems provide a convenient mechanism for rapid inactivation of almost any target protein of interest. Auxin-inducible degradation (AID) is one of the most common IPD systems and has been established in diverse eukaryotic research model organisms. Thus far, IPD tools have not been developed for use in pathogenic fungal species. Here, we demonstrate that the original AID and the second generation, AID2, systems work efficiently and rapidly in the human pathogenic yeasts, Candida albicans and Candida glabrata. We developed a collection of plasmids that support AID system use in laboratory strains of these pathogens. These systems can induce >95% degradation of target proteins within minutes. In the case of AID2, maximal degradation was achieved at low nanomolar concentrations of the synthetic auxin analog 5-adamantyl-indole-3-acetic acid. Auxin-induced target degradation successfully phenocopied gene deletions in both species. The system should be readily adaptable to other fungal species and to clinical pathogen strains. Our results define the AID system as a powerful and convenient functional genomics tool for protein characterization in fungal pathogens. IMPORTANCE Life-threatening fungal infections are an escalating human health problem, complicated by limited treatment options and the evolution of drug resistant pathogen strains. Identification of new targets for therapeutics to combat invasive fungal infections, including those caused by Candida species, is an urgent need. In this report, we establish and validate an inducible protein degradation methodology in Candida albicans and Candida glabrata that provides a new tool for protein functional characterization in these, and likely other, fungal pathogen species. We expect this tool will ultimately be useful for the identification and characterization of promising drug tar
Published: 2023

15. Acylation of glycerolipids in mycobacteria

Author: National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Kumar Angala, Shiva, Carreras-Gonzalez, Ana, Huc-Claustre, Emilie, Anso, Itxaso, Kaur, Devinder, Jones, Victoria, Palčeková, Zuzana, Belardinelli, Juan M., Sousa-d’Auria, Célia de, Shi, Libin, Slama, Nawel, Houssin, Christine, Quémard, Annaïk, McNeil, Michael, Guerin, Marcelo E., Jackson, Mary, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Kumar Angala, Shiva, Carreras-Gonzalez, Ana, Huc-Claustre, Emilie, Anso, Itxaso, Kaur, Devinder, Jones, Victoria, Palčeková, Zuzana, Belardinelli, Juan M., Sousa-d’Auria, Célia de, Shi, Libin, Slama, Nawel, Houssin, Christine, Quémard, Annaïk, McNeil, Michael, Guerin, Marcelo E., and Jackson, Mary
Abstract: We report on the existence of two phosphatidic acid biosynthetic pathways in mycobacteria, a classical one wherein the acylation of the sn-1 position of glycerol-3-phosphate (G3P) precedes that of sn-2 and another wherein acylations proceed in the reverse order. Two unique acyltransferases, PlsM and PlsB2, participate in both pathways and hold the key to the unusual positional distribution of acyl chains typifying mycobacterial glycerolipids wherein unsaturated substituents principally esterify position sn-1 and palmitoyl principally occupies position sn-2. While PlsM selectively transfers a palmitoyl chain to the sn-2 position of G3P and sn-1-lysophosphatidic acid (LPA), PlsB2 preferentially transfers a stearoyl or oleoyl chain to the sn-1 position of G3P and an oleyl chain to sn-2-LPA. PlsM is the first example of an sn-2 G3P acyltransferase outside the plant kingdom and PlsB2 the first example of a 2-acyl-G3P acyltransferase. Both enzymes are unique in their ability to catalyze acyl transfer to both G3P and LPA.
Published: 2023

16. Signatures of transmission in within-host M. tuberculosis variation

Author: National Institute of Allergy and Infectious Diseases (US), Comas, Iñaki [0000-0001-5504-9408], Walter, Katharine S., Cohen, Ted, Mathema, Barun, Colijn, Caroline, Sobkowiak, Benjamin, Comas, Iñaki, Goig, Galo A., Croda, Julio, Andrews, Jason R., National Institute of Allergy and Infectious Diseases (US), Comas, Iñaki [0000-0001-5504-9408], Walter, Katharine S., Cohen, Ted, Mathema, Barun, Colijn, Caroline, Sobkowiak, Benjamin, Comas, Iñaki, Goig, Galo A., Croda, Julio, and Andrews, Jason R.
Abstract: Background: Because M. tuberculosis evolves slowly, transmission clusters often contain multiple individuals with identical consensus genomes, making it difficult to reconstruct transmission chains. Finding additional sources of shared M. tuberculosis variation could help overcome this problem. Previous studies have reported M. tuberculosis diversity within infected individuals; however, whether within-host variation improves transmission inferences remains unclear. Methods: To evaluate the transmission information present in within-host M. tuberculosis variation, we re-analyzed publicly available sequence data from three household transmission studies, using household membership as a proxy for transmission linkage between donor-recipient pairs. Findings: We found moderate levels of minority variation present in M. tuberculosis sequence data from cultured isolates that varied significantly across studies (mean: 6, 7, and 170 minority variants above a 1% minor allele frequency threshold, outside of PE/PPE genes). Isolates from household members shared more minority variants than did isolates from unlinked individuals in the three studies (mean 98 shared minority variants vs. 10; 0.8 vs. 0.2, and 0.7 vs. 0.2, respectively). Shared within-host variation was significantly associated with household membership (OR: 1.51 [1.30,1.71], for one standard deviation increase in shared minority variants). Models that included shared within-host variation improved the accuracy of predicting household membership in all three studies as compared to models without within-host variation (AUC: 0.95 versus 0.92, 0.99 versus 0.95, and 0.93 versus 0.91). Interpretation: Within-host M. tuberculosis variation persists through culture and could enhance the resolution of transmission inferences. The substantial differences in minority variation recovered across studies highlights the need to optimize approaches to recover and incorporate within-host variation into automated phylogenetic and t
Published: 2023

17. Proposed European Competence Network on Mastocytosis—American Initiative in Mast Cell Diseases (ECNM-AIM) Response Criteria in Advanced Systemic Mastocytosis

Author: Charles and Ann Johnson Foundation, Josep Carreras Leukemia Foundation, National Institute of Allergy and Infectious Diseases (US), Gotlib, Jason, Schwaab, Juliana, Shomali, William, George, Tracy I., Radia, Deepti, Castells, Mariana, Carter, Melody C., Hartmann, Karin, Álvarez-Twos, Iván, Brockow, Knut, Bonadonna, Patrizia, Hermine, Olivier, Niedoszytko, Marek, Hoermann, Gregor, Sperr, Wolfgang R., Oude Elberink, Hanneke, Siebenhaar, Frank, Butterfield, Joseph H., Ustun, Celalettin, Zanotti, Roberta, Triggiani, Massimo, Schwartz, Lawrence B., Lyons, Jonathan J., Orfao, Alberto, Sotlar, Karl, Horny, Hans-Peter, Arock, Michel, Metcalfe, Dean D., Akin, Cem, Lübke, Johannes, Valent, Peter, Reiter, Andreas, Charles and Ann Johnson Foundation, Josep Carreras Leukemia Foundation, National Institute of Allergy and Infectious Diseases (US), Gotlib, Jason, Schwaab, Juliana, Shomali, William, George, Tracy I., Radia, Deepti, Castells, Mariana, Carter, Melody C., Hartmann, Karin, Álvarez-Twos, Iván, Brockow, Knut, Bonadonna, Patrizia, Hermine, Olivier, Niedoszytko, Marek, Hoermann, Gregor, Sperr, Wolfgang R., Oude Elberink, Hanneke, Siebenhaar, Frank, Butterfield, Joseph H., Ustun, Celalettin, Zanotti, Roberta, Triggiani, Massimo, Schwartz, Lawrence B., Lyons, Jonathan J., Orfao, Alberto, Sotlar, Karl, Horny, Hans-Peter, Arock, Michel, Metcalfe, Dean D., Akin, Cem, Lübke, Johannes, Valent, Peter, and Reiter, Andreas
Abstract: Advanced systemic mastocytosis (AdvSM) is characterized by the presence of KIT D816V and other somatic mutations (eg, in SRSF2, ASXL1, and RUNX1) in 95% and 60% to 70% of patients, respectively. The biological and clinical consequences of AdvSM include multilineage involvement (eg, associated hematologic neoplasm) in 60% to 80% of patients, variable infiltration and damage (C-findings) of predominantly bone marrow and visceral organs through affected mast cell (MC) and non-MC lineages, and elevated levels of serum tryptase. Recently, the treatment landscape has substantially changed with the introduction of the multikinase/KIT inhibitor midostaurin and the selective KIT D816V inhibitor avapritinib. In this review, we discuss the evolution of AdvSM response criteria that have been developed to better capture clinical benefit (eg, improved responses and progression-free and overall survival). We propose refined response criteria from European Competence Network on Mastocytosis and American Initiative in Mast Cell Diseases investigators that use a tiered approach to segregate the effects of histopathologic (eg, bone marrow MC burden, tryptase), molecular (eg, KIT D816V variant allele frequency), clinical (eg, C-findings), and symptom response on long-term outcomes. These response criteria require evaluation in future prospective clinical trials of selective KIT inhibitors and other novel agents.
Published: 2022

18. CryoEM structural exploration of catalytically active enzyme pyruvate carboxylase

Author: Human Frontier Science Program, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), National Institute of General Medical Sciences (US), National Institute of Allergy and Infectious Diseases (US), López-Alonso, Jorge P., Lázaro, Melisa, Gil-Cartón, David, Choi, Philip H., Dodu, Alexandra, Tong, Liang, Valle, Mikel, Human Frontier Science Program, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), National Institute of General Medical Sciences (US), National Institute of Allergy and Infectious Diseases (US), López-Alonso, Jorge P., Lázaro, Melisa, Gil-Cartón, David, Choi, Philip H., Dodu, Alexandra, Tong, Liang, and Valle, Mikel
Abstract: Pyruvate carboxylase (PC) is a tetrameric enzyme that contains two active sites per subunit that catalyze two consecutive reactions. A mobile domain with an attached prosthetic biotin links both reactions, an initial biotin carboxylation and the subsequent carboxyl transfer to pyruvate substrate to produce oxaloacetate. Reaction sites are at long distance, and there are several co-factors that play as allosteric regulators. Here, using cryoEM we explore the structure of active PC tetramers focusing on active sites and on the conformational space of the oligomers. The results capture the mobile domain at both active sites and expose catalytic steps of both reactions at high resolution, allowing the identification of substrates and products. The analysis of catalytically active PC tetramers reveals the role of certain motions during enzyme functioning, and the structural changes in the presence of additional cofactors expose the mechanism for allosteric regulation.
Published: 2022

19. WASp modulates RPA function on single-stranded DNA in response to replication stress and DNA damage

Author: National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Cancer Research UK, European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), University of Iowa, Han, Seong-Su, Wen, Kuo-Kuang, García-Rubio, María L., Wold, Mark S., Aguilera, Andrés, Niedzwiedz, Wojciech, Vyas, Yatin M., National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Cancer Research UK, European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), University of Iowa, Han, Seong-Su, Wen, Kuo-Kuang, García-Rubio, María L., Wold, Mark S., Aguilera, Andrés, Niedzwiedz, Wojciech, and Vyas, Yatin M.
Abstract: Perturbation in the replication-stress response (RSR) and DNA-damage response (DDR) causes genomic instability. Genomic instability occurs in Wiskott-Aldrich syndrome (WAS), a primary immunodeficiency disorder, yet the mechanism remains largely uncharacterized. Replication protein A (RPA), a single-strand DNA (ssDNA) binding protein, has key roles in the RSR and DDR. Here we show that human WAS-protein (WASp) modulates RPA functions at perturbed replication forks (RFs). Following genotoxic insult, WASp accumulates at RFs, associates with RPA, and promotes RPA:ssDNA complexation. WASp deficiency in human lymphocytes destabilizes RPA:ssDNA-complexes, impairs accumulation of RPA, ATR, ETAA1, and TOPBP1 at genotoxin-perturbed RFs, decreases CHK1 activation, and provokes global RF dysfunction. las17 (yeast WAS-homolog)-deficient S. cerevisiae also show decreased ScRPA accumulation at perturbed RFs, impaired DNA recombination, and increased frequency of DNA double-strand break (DSB)-induced single-strand annealing (SSA). Consequently, WASp (or Las17)-deficient cells show increased frequency of DSBs upon genotoxic insult. Our study reveals an evolutionarily conserved, essential role of WASp in the DNA stress-resolution pathway, such that WASp deficiency provokes RPA dysfunction-coupled genomic instability.
Published: 2022

20. Refined treatment response criteria for indolent systemic mastocytosis proposed by the ECNM-AIM consortium

Author: National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Medical University of Gdańsk, Austrian Science Fund, Pyatilova, Polina, Akin, Cem, Álvarez-Twose, Iván, Arock, Michel, Bonadonna, Patrizia, Brockow, Knut, Butterfield, Joseph H., Broesby-Olsen, Sigurd, Carter, Melody C., Castells, Mariana, George, Tracy I., Gotlib, Jason, Greiner, Georg, Gulen, Theo, Hartmann, Karin, Hermine, Olivier, Horny, Hans-Peter, Jawhar, Mohamad, Lange, Magdalena, Lyons, Jonathan J., Maurer, Marcus, Metcalfe, Dean D., Nedoszytko, Boguslaw, Niedoszytko, Marek, Orfao, Alberto, Reiter, Andreas, Schwaab, Juliana, Sotlar, Karl, Sperr, Wolfgang R., Triggiani, Massimo, Valent, Peter, Siebenhaar, Frank, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Medical University of Gdańsk, Austrian Science Fund, Pyatilova, Polina, Akin, Cem, Álvarez-Twose, Iván, Arock, Michel, Bonadonna, Patrizia, Brockow, Knut, Butterfield, Joseph H., Broesby-Olsen, Sigurd, Carter, Melody C., Castells, Mariana, George, Tracy I., Gotlib, Jason, Greiner, Georg, Gulen, Theo, Hartmann, Karin, Hermine, Olivier, Horny, Hans-Peter, Jawhar, Mohamad, Lange, Magdalena, Lyons, Jonathan J., Maurer, Marcus, Metcalfe, Dean D., Nedoszytko, Boguslaw, Niedoszytko, Marek, Orfao, Alberto, Reiter, Andreas, Schwaab, Juliana, Sotlar, Karl, Sperr, Wolfgang R., Triggiani, Massimo, Valent, Peter, and Siebenhaar, Frank
Abstract: Indolent systemic mastocytosis (ISM) has a favorable prognosis and normal life expectancy. However, many patients suffer from mast cell (MC) mediator-related symptoms, which significantly affect quality of life (QoL). Cutaneous, gastrointestinal, and neurological complaints, musculoskeletal pain, and the presence of skin lesions, anaphylaxis, and osteoporosis are the main symptoms and signs in ISM and must be assessed in all patients before and during treatment. Validated mastocytosis-specific patient-reported outcome measures (PROMs) should be used for this purpose. Serum tryptase and KIT D816V allele burden are recommended as secondary outcome parameters, noting that they do not reflect the severity of signs, symptoms, and related QoL impairment, but indirectly express MC burden. Changes from baseline of 90%, 60%, and 30% indicate complete response >90%, major response 60% to 90%, partial response 30% to 60%, and no response <30% to treatment. To conclude, we recommend the use of PROMs as primary outcome parameters to define treatment response in patients with ISM in clinical trials and in everyday clinical practice.
Published: 2022

21. Eosinophilia Associated With Immune Deficiency

Author: Job Research Foundation, Junta de Andalucía, Instituto de Salud Carlos III, National Institute of Allergy and Infectious Diseases (US), Olbrich, Peter, Ortiz‐Aljaro, Pilar, Freeman, Alexandra F., Job Research Foundation, Junta de Andalucía, Instituto de Salud Carlos III, National Institute of Allergy and Infectious Diseases (US), Olbrich, Peter, Ortiz‐Aljaro, Pilar, and Freeman, Alexandra F.
Abstract: The differential diagnosis of eosinophilia is broad and includes infections, malignancies, and atopy as well as inborn errors of immunity (IEI). Certain types of IEIs are known to be associated with elevated numbers of eosinophils and frequently elevated serum IgE, whereas for others the degree and frequency of eosinophilia are less established. The molecular defects underlying IEI are heterogeneous and affect different pathways, which highlights the complex regulations of this cell population within the immune system. In this review, we list and discuss clinical manifestations and therapies of immune deficiency or immune dysregulation disorders associated with peripheral blood or tissue eosinophilia with or without raised IgE levels. We present illustrative case vignettes for the most common entities and propose a diagnostic algorithm aiming to help physicians systematically to evaluate patients with eosinophilia and suspicion of an underlying IEI.
Published: 2022

22. Mutation L319Q in the PB1 Polymerase Subunit Improves Attenuation of a Candidate Live-Attenuated Influenza A Virus Vaccine

Author: New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), Department of Defense (US), Center for Research for Influenza Pathogenesis (US), Ministerio de Ciencia e Innovación (España), Icahn School of Medicine at Mount Sinai, Nogales, Aitor [0000-0002-2424-7900], Lowen, Anice C. [0000-0002-9829-112X], Chiem, Kevin [0000-0002-3892-5944], García-Sastre, Adolfo [0000-0002-6551-1827], Albrecht, Randy A. [0000-0003-4008-503X], Dewhurst, Stephen [0000-0001-7729-7920], Nogales, Aitor, Steel, John, Liu, Wen-Chun, Lowen, Anice C., Rodriguez, Laura, Chiem, Kevin, Cox, Andrew, García-Sastre, Adolfo, Albrecht, Randy A., Dewhurst, Stephen, Martínez-Sobrido, Luis, New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), Department of Defense (US), Center for Research for Influenza Pathogenesis (US), Ministerio de Ciencia e Innovación (España), Icahn School of Medicine at Mount Sinai, Nogales, Aitor [0000-0002-2424-7900], Lowen, Anice C. [0000-0002-9829-112X], Chiem, Kevin [0000-0002-3892-5944], García-Sastre, Adolfo [0000-0002-6551-1827], Albrecht, Randy A. [0000-0003-4008-503X], Dewhurst, Stephen [0000-0001-7729-7920], Nogales, Aitor, Steel, John, Liu, Wen-Chun, Lowen, Anice C., Rodriguez, Laura, Chiem, Kevin, Cox, Andrew, García-Sastre, Adolfo, Albrecht, Randy A., Dewhurst, Stephen, and Martínez-Sobrido, Luis
Abstract: Influenza A viruses (IAV) remain emerging threats to human public health. Live-attenuated influenza vaccines (LAIV) are one of the most effective prophylactic options to prevent disease caused by influenza infections. However, licensed LAIV remain restricted for use in 2- to 49-year-old healthy and nonpregnant people. Therefore, development of LAIV with increased safety, immunogenicity, and protective efficacy is highly desired. The U.S.-licensed LAIV is based on the master donor virus (MDV) A/Ann Arbor/6/60 H2N2 backbone, which was generated by adaptation of the virus to growth at low temperatures. Introducing the genetic signature of the U.S. MDV into the backbone of other IAV strains resulted in varying levels of attenuation. While the U.S. MDV mutations conferred an attenuated phenotype to other IAV strains, the same amino acid changes did not significantly attenuate the pandemic A/California/04/09 H1N1 (pH1N1) strain. To attenuate pH1N1, we replaced the conserved leucine at position 319 with glutamine (L319Q) in PB1 and analyzed the in vitro and in vivo properties of pH1N1 viruses containing either PB1 L319Q alone or in combination with the U.S. MDV mutations using two animal models of influenza infection and transmission, ferrets and guinea pigs. Our results demonstrated that L319Q substitution in the pH1N1 PB1 alone or in combination with the mutations of the U.S. MDV resulted in reduced pathogenicity (ferrets) and transmission (guinea pigs), and an enhanced temperature sensitive phenotype. These results demonstrate the feasibility of generating an attenuated MDV based on the backbone of a contemporary pH1N1 IAV strain. IMPORTANCE Vaccination represents the most effective strategy to reduce the impact of seasonal IAV infections. Although LAIV are superior in inducing protection and sterilizing immunity, they are not recommended for many individuals who are at high risk for severe disease. Thus, development of safer and more effective LAIV are needed. A concer
Published: 2022

23. Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

Author: Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Grifols, YoMeCorono, National Institutes of Health (US), Roddenberry Foundation, Defense Advanced Research Projects Agency (US), Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), Swiss National Science Foundation, Varona, José F., Landete, Pedro, López-Martín, José A., Estrada, Vicente, Paredes, Roger, Guisado Vasco, P., Fernández de Orueta, Lucía, Torralba, Miguel, Fortún, Jesús, Vates, Roberto, Barberán, José, Clotet, Bonaventura, Ancochea, Julio, Carnevali, Daniel, Cabello, Noemí, Porras, Lourdes, Gijón, Paloma, Monereo, Alfonso, Abad, Daniel, Zúñiga Lucas, Sonia, Solá Gurpegui, Isabel, Rodón, Jordi, Vergara-Alert, Júlia, Izquierdo-Useros, Núria, Fudio, Salvador, Pontes, María José, Rivas, Beatriz de, Girón de Velasco, Patricia, Nieto, Antonio, Gómez, Javier, Avilés, Pablo, Lubomirov, Rubin, Belgrano, Álvaro, Sopesén, Belén, White, Kris M., Rosales, Romel, Yildiz, Soner, Reuschl, Ann-Kathrin; Thorne, Lucy G.; Jolly, Claire; Towers, Greg J.; Zuliani-Alvarez, Lorena; Bouhaddou, Mehdi; Obernier, Kirsten; Enjuanes Sánchez, Luis CSIC ORCID ; Fernández-Sousa, José M.; Plitidepsin – COVID - 19 Study Group; Krogan, Nevan J.; Jimeno, José M.; García-Sastre, Adolfo, Reuschl, Ann-Kathrin, Thorne, Lucy G., Jolly, Claire, Towers, Greg J., Zuliani-Alvarez, Lorena, Bouhaddou, Mehdi, Obernier, Kirsten, McGovern, Briana L., Rodríguez, M. Luis, Enjuanes Sánchez, Luis, Fernández-Sousa, José M., Krogan, Nevan J., Jimeno, José M., García-Sastre, Adolfo, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Grifols, YoMeCorono, National Institutes of Health (US), Roddenberry Foundation, Defense Advanced Research Projects Agency (US), Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), Swiss National Science Foundation, Varona, José F., Landete, Pedro, López-Martín, José A., Estrada, Vicente, Paredes, Roger, Guisado Vasco, P., Fernández de Orueta, Lucía, Torralba, Miguel, Fortún, Jesús, Vates, Roberto, Barberán, José, Clotet, Bonaventura, Ancochea, Julio, Carnevali, Daniel, Cabello, Noemí, Porras, Lourdes, Gijón, Paloma, Monereo, Alfonso, Abad, Daniel, Zúñiga Lucas, Sonia, Solá Gurpegui, Isabel, Rodón, Jordi, Vergara-Alert, Júlia, Izquierdo-Useros, Núria, Fudio, Salvador, Pontes, María José, Rivas, Beatriz de, Girón de Velasco, Patricia, Nieto, Antonio, Gómez, Javier, Avilés, Pablo, Lubomirov, Rubin, Belgrano, Álvaro, Sopesén, Belén, White, Kris M., Rosales, Romel, Yildiz, Soner, Reuschl, Ann-Kathrin; Thorne, Lucy G.; Jolly, Claire; Towers, Greg J.; Zuliani-Alvarez, Lorena; Bouhaddou, Mehdi; Obernier, Kirsten; Enjuanes Sánchez, Luis CSIC ORCID ; Fernández-Sousa, José M.; Plitidepsin – COVID - 19 Study Group; Krogan, Nevan J.; Jimeno, José M.; García-Sastre, Adolfo, Reuschl, Ann-Kathrin, Thorne, Lucy G., Jolly, Claire, Towers, Greg J., Zuliani-Alvarez, Lorena, Bouhaddou, Mehdi, Obernier, Kirsten, McGovern, Briana L., Rodríguez, M. Luis, Enjuanes Sánchez, Luis, Fernández-Sousa, José M., Krogan, Nevan J., Jimeno, José M., and García-Sastre, Adolfo
Abstract: Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.
Published: 2022

24. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

Author: National Institutes of Health (US), National Center for Advancing Translational Sciences (US), National Human Genome Research Institute (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Pershing Square Foundation, Institut National de la Santé et de la Recherche Médicale (France), Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, Université de Paris, European Commission, Hellenic Foundation for Research and Innovation, Science Foundation Ireland, Regione Lazio, Generalitat de Catalunya, National Institute of Allergy and Infectious Diseases (US), Andreakos, Evangelos, Abel, Laurent, Vinh, Donald C., Kaja, Elżbieta, Drolet, Beth A., Zhang, Qian, O’Farrelly, Cliona, Novelli, Giuseppe, Rodríguez-Gallego, Carlos, Haerynck, Filomeen, Prando, Carolina, Pujol, Aurora, COVID Human Genetic Effort, Su, Helen C., Casanova, Jean-Laurent, Spaan, András N., National Institutes of Health (US), National Center for Advancing Translational Sciences (US), National Human Genome Research Institute (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Pershing Square Foundation, Institut National de la Santé et de la Recherche Médicale (France), Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, Université de Paris, European Commission, Hellenic Foundation for Research and Innovation, Science Foundation Ireland, Regione Lazio, Generalitat de Catalunya, National Institute of Allergy and Infectious Diseases (US), Andreakos, Evangelos, Abel, Laurent, Vinh, Donald C., Kaja, Elżbieta, Drolet, Beth A., Zhang, Qian, O’Farrelly, Cliona, Novelli, Giuseppe, Rodríguez-Gallego, Carlos, Haerynck, Filomeen, Prando, Carolina, Pujol, Aurora, COVID Human Genetic Effort, Su, Helen C., Casanova, Jean-Laurent, and Spaan, András N.
Abstract: SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.
Published: 2022

25. Standards of genetic testing in the diagnosis and prognostication of systemic mastocytosis in 2022: Recommendations of the EU-US cooperative group

Author: National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Austrian Science Fund, Hoermann, Gregor, Sotlar, Karl, Jawhar, Mohamad, Kristensen, Thomas K., Bachelot, Guillaume, Nedoszytko, Boguslaw, Carter, Melody C., Horny, Hans-Peter, Bonadonna, Patrizia, Sperr, Wolfgang R., Hartmann, Karin, Brockow, Knut, Lyons, Jonathan J., Kluin-Nelemans, Hanneke C., Hermine, Olivier, Akin, Cem, Broesby-Olsen, Sigurd, Triggiani, Massimo, Butterfield, Joseph H., Schwaab, Juliana, Arock, Michel, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Austrian Science Fund, Hoermann, Gregor, Sotlar, Karl, Jawhar, Mohamad, Kristensen, Thomas K., Bachelot, Guillaume, Nedoszytko, Boguslaw, Carter, Melody C., Horny, Hans-Peter, Bonadonna, Patrizia, Sperr, Wolfgang R., Hartmann, Karin, Brockow, Knut, Lyons, Jonathan J., Kluin-Nelemans, Hanneke C., Hermine, Olivier, Akin, Cem, Broesby-Olsen, Sigurd, Triggiani, Massimo, Butterfield, Joseph H., Schwaab, Juliana, and Arock, Michel
Abstract: Mastocytosis comprises rare heterogeneous diseases characterized by an increased accumulation of abnormal mast cells in various organs/tissues. The pathogenesis of mastocytosis is strongly linked to the presence of KIT-activating mutations. In systemic mastocytosis (SM), the most frequent mutation encountered is KIT p.D816V, whose presence constitutes one of the minor diagnostic criteria. Different techniques are used to search and quantify the KIT p.D816V mutant; however, allele-specific quantitative PCR and droplet digital PCR are today the most sensitive. The analysis of the KIT p.D816V allele burden has undeniable interest for diagnostic, prognostic, and therapeutic monitoring. The analysis of non–mast cell hematological compartments in SM is similarly important because KIT p.D816V multilineage involvement is associated with a worse prognosis. In addition, in advanced forms of SM, mutations in genes other than KIT are frequently identified and affect negatively disease outcome and response to therapy. Thus, combined quantitative and sensitive analysis of KIT mutations and next-generation sequencing of other recurrently involved myeloid genes make it possible to better characterize the extent of the affected cellular compartments and additional molecular aberrations, providing a more detailed overview of the complex mutational landscape of SM, in relation with the clinical heterogeneity of the disease. In this article, we report the latest recommendations of the EU-US Cooperative Group presented in September 2020 in Vienna during an international working conference, on the techniques we consider standard to detect and quantify the KIT p.D816V mutant in SM and additional myeloid mutations found in SM subtypes.
Published: 2022

26. Standards of pathology in the diagnosis of systemic mastocytosis: recommendations of the EU-US cooperative group

Author: Swiss National Science Foundation, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Austrian Science Fund, Sotlar, Karl, George, Tracy I., Kluin, Philip, Reiter, Andreas, Schwaab, Juliana, Panse, Jens, Brockow, Knut, Hartmann, Karin, Sperr, Wolfgang R., Kristensen, Thomas K., Nedoszytko, Boguslaw, Carter, Melody C., Bonadonna, Patrizia, Lyons, Jonathan J., Kluin-Nelemans, Hanneke C., Hermine, Olivier, Akin, Cem, Broesby-Olsen, Sigurd, Hoermann, Gregor, Triggiani, Massimo, Horny, Hans-Peter, Swiss National Science Foundation, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Austrian Science Fund, Sotlar, Karl, George, Tracy I., Kluin, Philip, Reiter, Andreas, Schwaab, Juliana, Panse, Jens, Brockow, Knut, Hartmann, Karin, Sperr, Wolfgang R., Kristensen, Thomas K., Nedoszytko, Boguslaw, Carter, Melody C., Bonadonna, Patrizia, Lyons, Jonathan J., Kluin-Nelemans, Hanneke C., Hermine, Olivier, Akin, Cem, Broesby-Olsen, Sigurd, Hoermann, Gregor, Triggiani, Massimo, and Horny, Hans-Peter
Abstract: Pathology plays a central role in the diagnosis of systemic mastocytosis (SM), its delineation from other neoplasms and reactive conditions, and in monitoring of SM under therapy. The morphologic hallmark of SM is the accumulation of spindle-shaped, hypogranulated mast cells (MCs) in bone marrow (BM) and other extracutaneous tissues. Four of the 5 World Health Organization–defined diagnostic criteria (ie, compact MC aggregates [=major criterion]; atypical MC morphology; activating KIT point mutations; aberrant expression of CD25 and/or CD2 and/or CD30 in MCs [=minor criteria]) can be addressed by the pathologist. The final classification of SM variants as either BM mastocytosis, indolent SM, smoldering SM, aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN), or MC leukemia (MCL) has important prognostic significance and requires the integration of certain morphological, clinical, radiological, and biochemical data, referred to as B- and C-findings. Substantial diagnostic challenges may be posed to the pathologist and clinician especially in the so-called advanced SM variants, that is, ASM, MCL, and SM-AHN. In this article, updated recommendations of the EU-US Cooperative Group regarding standards of pathology in the diagnosis of SM, presented during the year 2020 Working Conference held in September in Vienna, are reported.
Published: 2022

27. Evolution of influenza A virus in intensive and free-range swine farms in Spain

Author: National Institute of Allergy and Infectious Diseases (US), Center for Research for Influenza Pathogenesis (US), Centers of Excellence for Influenza Research and Surveillance (US), Center of Excellence for Influenza Research and Response (US), Encinas, Paloma [0000-0001-9596-8070], Del Real Soldevilla, Gustavo [0000-0002-8171-2274], García-Sastre, Adolfo [0000-0002-6551-1827], Encinas, Paloma, Del Real Soldevilla, Gustavo, Dutta, Jayeeta, Khan, Zenab, van Bakel, Harm, Martín del Burgo, M. Ángeles, García-Sastre, Adolfo, Nelson, Martha, National Institute of Allergy and Infectious Diseases (US), Center for Research for Influenza Pathogenesis (US), Centers of Excellence for Influenza Research and Surveillance (US), Center of Excellence for Influenza Research and Response (US), Encinas, Paloma [0000-0001-9596-8070], Del Real Soldevilla, Gustavo [0000-0002-8171-2274], García-Sastre, Adolfo [0000-0002-6551-1827], Encinas, Paloma, Del Real Soldevilla, Gustavo, Dutta, Jayeeta, Khan, Zenab, van Bakel, Harm, Martín del Burgo, M. Ángeles, García-Sastre, Adolfo, and Nelson, Martha
Abstract: Swine harbor genetically diverse influenza A viruses (IAVs) with the capacity to host-switch to humans, causing global pandemics. Spain is the largest swine producer in Europe and has a mixed production system that includes 'white coat' pigs raised intensively in modern buildings and free-range Iberian pigs that interface differently with humans, wildlife, and other swine. Through active longitudinal IAV surveillance in nine Spanish provinces during 2015-9, we generated forty-seven complete or near-complete genome sequences from IAVs collected from swine in both systems. Genetically diverse IAVs were identified in intensively raised white pigs and free-range Iberian pigs, including new H3N1 reassortants. Both systems are dynamic environments for IAV evolution, but driven by different processes. IAVs in white pigs were genetically related to viruses found in swine raised intensively in other European countries, reflecting high rates of viral introduction following European trade routes. In contrast, IAVs in Iberian pigs have a genetic makeup shaped by frequent introductions of human IAVs, reflecting rearing practices with high rates of human contact. Transmission between white and Iberian pigs also occurred. In conclusion, Iberian swine with high rates of human contact harbor genetically diverse IAVs and potentially serve as intermediary hosts between white pigs and humans, presenting an understudied zoonotic risk that requires further investigation.
Published: 2021

28. Signatures of immune selection in intact and defective proviruses distinguish HIV-1 elite controllers

Author: National Institutes of Health (US), Bill & Melinda Gates Foundation, Foundation for AIDS Research, Consejo Superior de Investigaciones Científicas (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Harvard University, University of California, Centers for AIDS Research (US), National Institute of Allergy and Infectious Diseases (US), National Cancer Institute (US), Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Heart, Lung, and Blood Institute (US), National Institute on Drug Abuse (US), National Institute of Mental Health (US), Delaney AIDS Research Enterprise, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology, Schwartz Family Foundation, Frederick National Laboratory for Cancer Research (US), Lian, Xiaodong, Gao, Ce, Sun, Xiaoming, Jiang, Chenyang, Einkauf, Kevin B., Seiger, Kyra W., Chevalier, Joshua M., Yuki, Yuko, Martin, Maureen, Hoh, Rebecca, Peluso, Michael J., Carrington, Mary, Ruiz-Mateos, Ezequiel, Deeks, Steven G., Rosenberg, Eric S, Walker, Bruce D., Lichterfeld, Mathias, Yu, Xu G., National Institutes of Health (US), Bill & Melinda Gates Foundation, Foundation for AIDS Research, Consejo Superior de Investigaciones Científicas (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Harvard University, University of California, Centers for AIDS Research (US), National Institute of Allergy and Infectious Diseases (US), National Cancer Institute (US), Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Heart, Lung, and Blood Institute (US), National Institute on Drug Abuse (US), National Institute of Mental Health (US), Delaney AIDS Research Enterprise, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology, Schwartz Family Foundation, Frederick National Laboratory for Cancer Research (US), Lian, Xiaodong, Gao, Ce, Sun, Xiaoming, Jiang, Chenyang, Einkauf, Kevin B., Seiger, Kyra W., Chevalier, Joshua M., Yuki, Yuko, Martin, Maureen, Hoh, Rebecca, Peluso, Michael J., Carrington, Mary, Ruiz-Mateos, Ezequiel, Deeks, Steven G., Rosenberg, Eric S, Walker, Bruce D., Lichterfeld, Mathias, and Yu, Xu G.
Abstract: Increasing evidence suggests that durable drug-free control of HIV-1 replication is enabled by effective cellular immune responses that may induce an attenuated viral reservoir configuration with a weaker ability to drive viral rebound. Here, we comprehensively tracked effects of antiviral immune responses on intact and defective proviral sequences from elite controllers (ECs), analyzing both classical escape mutations and HIV-1 chromosomal integration sites as biomarkers of antiviral immune selection pressure. We observed that, within ECs, defective proviruses were commonly located in permissive genic euchromatin positions, which represented an apparent contrast to autologous intact proviruses that were frequently located in heterochromatin regions; this suggests differential immune selection pressure on intact versus defective proviruses in ECs. In comparison to individuals receiving antiretroviral therapy, intact and defective proviruses from ECs showed reduced frequencies of escape mutations in cytotoxic T cell epitopes and antibody contact regions, possibly due to the small and poorly inducible reservoir that may be insufficient to drive effective viral escape in ECs. About 15% of ECs harbored nef deletions in intact proviruses, consistent with increased viral vulnerability to host immunity in the setting of nef dysfunction. Together, these results suggest a distinct signature of immune footprints in proviral sequences from ECs.
Published: 2021

29. Proceedings from the Inaugural American Initiative in Mast Cell Diseases (AIM) Investigator Conference

Author: National Institutes of Health (US), Charles and Ann Johnson Foundation, National Institute of Allergy and Infectious Diseases (US), American Academy of Allergy Asthma and Immunology, Austrian Science Fund, Gotlib, Jason, George, Tracy I., Carter, Melody C., Austen, K. Frank, Bochner, Bruce, Dwyer, Daniel, Lyons, Jonathan J., Hamilton, Matthew J., Butterfield, Joseph H., Bonadonna, Patrizia, Weiler, Catherine, Galli, Stephen J., Schwartz, Lawrence B., Oude Elberink, Hanneke, Maitland, Anne, Theoharides, Theoharis, Ustun, Celalettin, Horny, Hans-Peter, Orfao, Alberto, Deininger, Michael, Radia, Deepti, Jawhar, Mohamad, Kluin-Nelemans, Hanneke C., Metcalfe, Dean D., Arock, Michel, Sperr, Wolfgang R., Valent, Peter, Castells, Mariana, Akin, Cem, National Institutes of Health (US), Charles and Ann Johnson Foundation, National Institute of Allergy and Infectious Diseases (US), American Academy of Allergy Asthma and Immunology, Austrian Science Fund, Gotlib, Jason, George, Tracy I., Carter, Melody C., Austen, K. Frank, Bochner, Bruce, Dwyer, Daniel, Lyons, Jonathan J., Hamilton, Matthew J., Butterfield, Joseph H., Bonadonna, Patrizia, Weiler, Catherine, Galli, Stephen J., Schwartz, Lawrence B., Oude Elberink, Hanneke, Maitland, Anne, Theoharides, Theoharis, Ustun, Celalettin, Horny, Hans-Peter, Orfao, Alberto, Deininger, Michael, Radia, Deepti, Jawhar, Mohamad, Kluin-Nelemans, Hanneke C., Metcalfe, Dean D., Arock, Michel, Sperr, Wolfgang R., Valent, Peter, Castells, Mariana, and Akin, Cem
Abstract: The American Initiative in Mast Cell Diseases (AIM) held its inaugural investigator conference at Stanford University School of Medicine in May 2019. The overarching goal of this meeting was to establish a Pan-American organization of physicians and scientists with multidisciplinary expertise in mast cell disease. To serve this unmet need, AIM envisions a network where basic, translational, and clinical researchers could establish collaborations with both academia and biopharma to support the development of new diagnostic methods, enhanced understanding of the biology of mast cells in human health and disease, and the testing of novel therapies. In these AIM proceedings, we highlight selected topics relevant to mast cell biology and provide updates regarding the recently described hereditary alpha-tryptasemia. In addition, we discuss the evaluation and treatment of mast cell activation (syndromes), allergy and anaphylaxis in mast cell disorders, and the clinical and biologic heterogeneity of the more indolent forms of mastocytosis. Because mast cell disorders are relatively rare, AIM hopes to achieve a coordination of scientific efforts not only in the Americas but also in Europe by collaborating with the well-established European Competence Network on Mastocytosis.
Published: 2021

30. Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

Author: Swiss National Science Foundation, European Commission, University of Basel, ETH Zurich, National Institute of General Medical Sciences (US), National Institute of Allergy and Infectious Diseases (US), Burroughs Wellcome Fund, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Howard Hughes Medical Institute, Hodcroft, Emma B. [0000-0002-0078-2212], Zuber, Moira [0000-0002-4275-8739], Nadeau, Sarah [0000-0003-1008-8918], Vaughan, Timothy G. [0000-0001-6220-2239], Crawford, Katharine H. D. [0000-0002-6223-4019], Althaus, Christian L. [0000-0002-5230-6760], Reichmuth, Martina L. [0000-0001-9345-851X], Bowen, John E. [0000-0003-3590-9727], Walls, Alexandra C. [0000-0002-9636-8330], Corti, Davide [0000-0002-5797-1364], Bloom, Jesse D. [0000-0003-1267-3408], Veesler, David [0000-0002-6019-8675], Mateo, David [0000-0002-1590-4163], Hernando de Castro, Alberto [0000-0003-1180-1068], Comas, Iñaki [0000-0001-5504-9408], González-Candelas, Fernando [0000-0002-0879-5798], Stadler, Tanja [0000-0001-6431-535X], Neher, Richard A. [0000-0003-2525-1407], Hodcroft, Emma B., Zuber, Moira, Nadeau, Sarah, Vaughan, Timothy G., Crawford, Katharine H. D., Althaus, Christian L., Reichmuth, Martina L., Bowen, John E., Walls, Alexandra C., Corti, Davide, Bloom, Jesse D., Veesler, David, Mateo, David, Hernando de Castro, Alberto, Comas, Iñaki, González-Candelas, Fernando, Seqcovid-Spain Consortium, Stadler, Tanja, Neher, Richard A., Swiss National Science Foundation, European Commission, University of Basel, ETH Zurich, National Institute of General Medical Sciences (US), National Institute of Allergy and Infectious Diseases (US), Burroughs Wellcome Fund, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Howard Hughes Medical Institute, Hodcroft, Emma B. [0000-0002-0078-2212], Zuber, Moira [0000-0002-4275-8739], Nadeau, Sarah [0000-0003-1008-8918], Vaughan, Timothy G. [0000-0001-6220-2239], Crawford, Katharine H. D. [0000-0002-6223-4019], Althaus, Christian L. [0000-0002-5230-6760], Reichmuth, Martina L. [0000-0001-9345-851X], Bowen, John E. [0000-0003-3590-9727], Walls, Alexandra C. [0000-0002-9636-8330], Corti, Davide [0000-0002-5797-1364], Bloom, Jesse D. [0000-0003-1267-3408], Veesler, David [0000-0002-6019-8675], Mateo, David [0000-0002-1590-4163], Hernando de Castro, Alberto [0000-0003-1180-1068], Comas, Iñaki [0000-0001-5504-9408], González-Candelas, Fernando [0000-0002-0879-5798], Stadler, Tanja [0000-0001-6431-535X], Neher, Richard A. [0000-0003-2525-1407], Hodcroft, Emma B., Zuber, Moira, Nadeau, Sarah, Vaughan, Timothy G., Crawford, Katharine H. D., Althaus, Christian L., Reichmuth, Martina L., Bowen, John E., Walls, Alexandra C., Corti, Davide, Bloom, Jesse D., Veesler, David, Mateo, David, Hernando de Castro, Alberto, Comas, Iñaki, González-Candelas, Fernando, Seqcovid-Spain Consortium, Stadler, Tanja, and Neher, Richard A.
Abstract: Following its emergence in late 2019, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2 has been tracked via phylogenetic analysis of viral genome sequences in unprecedented detail3–5. While the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, within Europe travel resumed in the summer of 2020. Here we report on a novel SARS-CoV-2 variant, 20E (EU1), that emerged in Spain in early summer, and subsequently spread across Europe. We find no evidence of increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate 20E (EU1) was introduced hundreds of times to European countries by summertime travelers, likely undermining local efforts to keep SARS-CoV-2 cases low. Our results demonstrate how a variant can rapidly become dominant even in absence of a substantial transmission advantage in favorable epidemiological settings. Genomic surveillance is critical to understanding how travel can impact SARS-CoV-2 transmission, and thus for informing future containment strategies as travel resumes.
Published: 2021

31. Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes

Author: Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases (US), National Institute of Allergy and Infectious Diseases (US), National Institute of Child Health and Human Development (US), National Institute of Environmental Health Sciences (US), Centers for Disease Control and Prevention (US), National Institutes of Health (US), Balzano-Nogueira, Leandro, Ramirez, Ricardo, Zamkovaya, Tatyana, Dailey, Jordan, Ardissone, Alexandria N., Chamala, Srikar, Serrano-Quílez, Joan, Rubio, Teresa, Haller, Michael J., Concannon, Patrick, Atkinson, Mark A., Schatz, Desmond A., Triplett, Eric W., Conesa, Ana, Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases (US), National Institute of Allergy and Infectious Diseases (US), National Institute of Child Health and Human Development (US), National Institute of Environmental Health Sciences (US), Centers for Disease Control and Prevention (US), National Institutes of Health (US), Balzano-Nogueira, Leandro, Ramirez, Ricardo, Zamkovaya, Tatyana, Dailey, Jordan, Ardissone, Alexandria N., Chamala, Srikar, Serrano-Quílez, Joan, Rubio, Teresa, Haller, Michael J., Concannon, Patrick, Atkinson, Mark A., Schatz, Desmond A., Triplett, Eric W., and Conesa, Ana
Abstract: Background: The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time. Results: We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion. At this time, abnormalities in lipid metabolism, decreased capacity for nutrient absorption, and intracellular ROS accumulation are detected in children progressing towards IA. Additionally, extracellular matrix remodeling, inflammation, cytotoxicity, angiogenesis, and increased activity of antigen-presenting cells are observed, which may contribute to beta cell destruction. Our results indicate that altered molecular homeostasis is present in IA-developing children months before the actual detection of islet autoantibodies, which opens an interesting window of opportunity for therapeutic intervention. Conclusions: The approach employed herein for assessment of the TEDDY cohort showcases the utilization of multi-omics data for the modeling of complex, multifactorial diseases, like T1D.
Published: 2021

32. 2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales

Author: National Institute of Allergy and Infectious Diseases (US), National Cancer Institute (US), National Institutes of Health (US), Frederick National Laboratory for Cancer Research (US), US Department of Homeland Security, National Institute of Food and Agriculture (US), Kuhn, Jens H. [0000-0002-7800-6045], Adkins, Scott [0000-0003-0095-8414], Alioto, Daniela [0000-0002-4954-8363], Alkhovsky, Sergey V. [0000-0001-6913-5841], Amarasinghe, Gaya K. [0000-0002-0418-9707], Avsic-Zupanc, Tatjana [0000-0001-6243-0688], Ayllón, María A. [0000-0001-7893-6106], Bahl, Justin [0000-0001-7572-4300], Balkema-Buschmann, A. [0000-0001-7613-9592], Ballinger, Matthew J. [0000-0001-7453-8725], Bartonička, Tomáš [0000-0001-7335-2435], Basler, Christopher F. [0000-0003-4195-425X], Bavari, Sina [0000-0001-8424-5635], Beer, Martin [0000-0002-0598-5254], Bente, Dennis A. [0000-0002-5150-7368], Bergeron, Éric [0000-0003-3398-8628], Bird, Brian H. [0000-0001-8170-8710], Blair, Carol D. [0000-0002-2803-0354], Blasdell, Kim R. [0000-0003-2121-0376], Bradfute, Steven B. [0000-0002-1985-751X], Breyta, Rachel [0000-0002-9106-1014], Briese, Thomas [0000-0002-4819-8963], Brown, Paul A. [0000-0002-6697-7688], Buchholz, Ursula J. [0000-0002-2329-3198], Buchmeier, Michael J. [0000-0002-2387-9287], Bukreyev, Alexander [0000-0002-0342-4824], Burt, Felicity [0000-0002-7238-7799], Buzkan, Nihal [0000-0002-0428-0447], Calisher, Charles H. [0000-0003-0213-294X], Cao, Mengji [0000-0003-0396-262X], Casas, Inmaculada [0000-0003-1840-1198], Chamberlain, John [0000-0002-7387-6420], Chandran, Kartik [0000-0003-0232-7077], Charrel, Rémi N. [0000-0002-7675-8251], Chen, Biao [0000-0002-2450-9296], Chiumenti, Michela [0000-0002-8412-3037], Choi, Il-Ryong [0000-0002-8035-7573], Clegg, J Christopher S. [0000-0003-3765-1862], Crozier, Ian [0000-0003-2485-4011], da Graça, John V. [0000-0003-0743-1519], Dávila, Alberto M.R. [0000-0002-6918-7673], de la Torre, J. C. [0000-0002-8171-8115], de Lamballerie, Xavier [0000-0001-7895-2720], De Swart, Rik L. [0000-0003-3599-8969], Di Bello, Patrick L. [0000-0002-4773-8040], Di Paola, Nicholas [0000-0002-9694-3913], Di Serio, Francesco [0000-0003-2822-704X], Dietzgen, Ralf G. [0000-0002-7772-2250], Digiaro, Michele [0009-0006-3089-3606], Dolja, Valerian V. [0000-0002-8148-4670], Dolnik, Olga [0000-0001-7739-4798], Drexler, J. Felix [0000-0002-3509-0232], Dürrwald, Ralf [0000-0002-3432-0438], Dufkova, Lucie [0000-0001-7302-2057], Dundon, William G. [0000-0002-2776-169X], Duprex, W. Paul [0000-0003-1716-6376], Dye, John M. [0000-0002-0883-5016], Easton, Andrew J. [0000-0002-2288-3882], Ebihara, Hideki [0000-0002-2576-9735], Elbeaino, Toufic [0000-0003-2211-7907], Ergünay, Koray [0000-0001-5422-1982], Fernandes, Jorlan [0000-0002-5039-0604], Fooks, Anthony R. [0000-0002-3243-6154], Formenty, Pierre B.H. [0000-0002-9482-5411], Forth, Leonie F [0000-0002-2708-2515], Fouchier, Ron A.M. [0000-0001-8095-2869], Freitas-Astúa, Juliana [0000-0002-0506-6880], Gago-Zachert, Selma [0000-0002-1084-2119], Gāo, George Fú [0000-0002-3869-615X], García, María Laura [0000-0001-6468-6943], García-Sastre, Adolfo [0000-0002-6551-1827], Garrison, Aura R. [0000-0003-3034-6400], Gbakima, Aiah [0000-0002-7642-0752], Goldstein, Tracey [0000-0002-1672-7410], Gonzalez, Jean-Paul J. [0000-0003-3063-1770], Griffiths, Anthony [0000-0001-5435-8364], Groschup, M. H. [0000-0003-0215-185X], Günther, Stephan [0000-0002-6562-0230], Guterres, Alexandro [0000-0001-8323-1477], Hall, Roy A. [0000-0001-5778-1387], Hammond, John [0000-0001-7593-747X], Hassan, Mohamed [0000-0002-1289-0878], Hepojoki, Jussi [0000-0001-5699-214X], Hepojoki, Satu [0000-0002-0696-1879], Hetzel, Udo [0000-0001-9142-560X], Hewson, Roger [0000-0003-2273-3152], Höper, Dirk [0000-0001-8408-2274], Horie, Masayuki [0000-0003-4682-7698], Hyndman, Timothy [0000-0002-7047-5023], Hughes, Holly R. [0000-0003-1380-8263], Hyndman, Timothy [0000-0003-4083-562X], Jambai, Amara [0000-0003-3754-2500], Jardim, Rodrigo [0000-0002-0943-5356], Jiāng, Dàohóng [0000-0002-3862-7461], Jonson, Gilda B. [0000-0003-0097-8634], Junglen, Sandra [0000-0002-3799-6011], Klempa, B. [0000-0002-6931-1224], Klingström, Jonas [0000-0001-9076-1441], Kobinger, Gary [0000-0003-0612-2298], Kondō, Hideki [0000-0001-9220-5350], Koonin, Eugene V. [0000-0003-3943-8299], Krupovic, Mart [0000-0001-5486-0098], Kurath, Gael [0000-0003-3294-560X], Laenen, Lies [0000-0001-9118-8608], Langevin, Stanley L. [0000-0002-6833-271X], Lee, Benhur [0000-0003-0760-1709], Lemos, Elba R.S. [0000-0003-3761-0200], Lukashevich, Igor S. [0000-0001-6523-5116], Maes, Piet [0000-0002-4571-5232], Marklewitz, Marco [0000-0003-1828-8770], Marzano, Shin-Yi L. [0000-0003-0548-3761], Mielke-Ehret, Nicole [0000-0003-0096-0696], Minafra, Angelantonio [0000-0002-0547-7129], Minutolo, Maria [0000-0001-7816-2657], Mühlberger, Elke [0000-0003-3547-9376], Naidu, Rayapati [0000-0002-7273-5116], Natsuaki, Tomohide [0000-0003-1823-7308], Navarro, José A. [0000-0002-0536-6074], Netesov, Sergey V. [0000-0002-7786-2464], Neumann, Gabriele [0000-0001-7054-1775], Nowotny, N. [0000-0002-3548-571X], Nunes, Márcio R.T. [0000-0003-0529-0230], Nylund, Are [0000-0002-1932-6604], Okland, Arnfinn Lodden [0000-0003-3062-4386], Oliveira, Renata C. [0000-0002-1904-7533], Pallás, Vicente [0000-0003-4954-989X], Pályi, Bernadett [0000-0003-1975-4198], Parrish, Colin R. [0000-0002-1836-6655], Pauvolid-Corrêa, Alex [0000-0002-6924-157X], Pawęska, Janusz T. [0000-0001-8776-7519], Radoshitzky, Sheli R. [0000-0001-8976-8056], Rahman, Aziz-Ul [0000-0002-3342-4462], Ramos-González, Pedro L. [0000-0002-9640-6587], Resende, Renato O. [0000-0003-3852-1576], Romanowski, Víctor [0000-0001-6378-7929], Robles Luna, Gabriel [0000-0003-3409-5557], Rota, Paul [0000-0002-8595-4094], Rubbenstroth, Dennis [0000-0002-8209-6274], Runstadler, Jonathan A. [0000-0002-6747-7765], Ruzek, Daniel [0000-0003-4655-2380], Sabanadzovic, Sead [0000-0002-2995-2633], Salát, Jiří [0000-0002-9915-8953], Sarpkaya, Kamil [0000-0001-5794-668X], Sasaya, Takahide [0000-0002-5020-9377], Shabbir, Muhammad Z. [0000-0003-4908-3313], Shí, Zhènglì [0000-0002-7309-6838], Sironi, Manuela [0000-0002-2267-5266], Smither, Sophie [0000-0002-7835-3581], Smura, Teemu [0000-0002-9187-3151], Spann, Kirsten [0000-0003-0567-8382], Spengler, Jessica R. [0000-0002-5383-0513], Stenglein, Mark D. [0000-0002-0993-813X], Takada, Ayato [0000-0003-2464-6642], Tesh, Robert B. [0000-0002-9226-397X], Thornburg, Natalie J. [0000-0003-3523-3616], Tomonaga, Keizō [0000-0003-0405-7103], Tordo, Noël [0000-0001-5873-059X], Towner, Jonathan S. [0000-0002-6473-3049], Turina, Massimo [0000-0002-9659-9470], Tzanetakis, Ioannis E. [0000-0002-5970-1763], Ulrich, R. G. [0000-0002-5620-1528], Vaira, Anna Maria [0000-0003-2526-4419], Van den Hoogen, Bernadette [0000-0003-1996-8559], Varsani, Arvind [0000-0003-4111-2415], Verbeek, Martin [0000-0002-8973-3803], Wahl, Victoria [0000-0002-6588-4308], Whitfield, Anna E. [0000-0002-3538-015X], Wolf, Yuri I. [0000-0002-0247-8708], Yutin, Natalya [0000-0002-3633-5123], Zerbini, F. Murilo [0000-0001-8617-0200], Kuhn, Jens H., Adkins, Scott, Alioto, Daniela, Alkhovsky, Sergey V., Amarasinghe, Gaya K., Anthony, Simon J., Avsic-Zupanc, Tatjana, Ayllón, María A., Bahl, Justin, Balkema-Buschmann, A., Ballinger, Matthew J., Bartonička, Tomáš, Basler, Christopher F., Bavari, Sina, Beer, Martin, Bente, Dennis A., Bergeron, Éric, Bird, Brian H., Blair, Carol D., Blasdell, Kim R., Bradfute, Steven B., Breyta, Rachel, Briese, Thomas, Brown, Paul A., Buchholz, Ursula J., Buchmeier, Michael J., Bukreyev, Alexander, Burt, Felicity, Buzkan, Nihal, Calisher, Charles H., Cao, Mengji, Casas, Inmaculada, Chamberlain, John, Chandran, Kartik, Charrel, Rémi N., Chen, Biao, Chiumenti, Michela, Choi, Il-Ryong, Clegg, J Christopher S., Crozier, Ian, da Graça, John V., Dal Bó, Elena, Dávila, Alberto M.R., de la Torre, J. C., de Lamballerie, Xavier, De Swart, Rik L., Di Bello, Patrick L., Di Paola, Nicholas, Di Serio, Francesco, Dietzgen, Ralf G., Digiaro, Michele, Dolja, Valerian V., Dolnik, Olga, Drebot, Michael A., Drexler, J. Felix, Dürrwald, Ralf, Dufkova, Lucie, Dundon, William G., Duprex, W. Paul, Dye, John M., Easton, Andrew J., Ebihara, Hideki, Elbeaino, Toufic, Ergünay, Koray, Fernandes, Jorlan, Fooks, Anthony R., Formenty, Pierre B.H., Forth, Leonie F., Fouchier, Ron A.M., Freitas-Astúa, Juliana, Gago-Zachert, Selma, Gāo, George Fú, García, María Laura, García-Sastre, Adolfo, Garrison, Aura R., Gbakima, Aiah, Goldstein, Tracey, Gonzalez, Jean-Paul J., Griffiths, Anthony, Groschup, M. H., Günther, Stephan, Guterres, Alexandro, Hall, Roy A., Hammond, John, Hassan, Mohamed, Hepojoki, Jussi, Hepojoki, Satu, Hetzel, Udo, Hewson, Roger, Hoffmann, Bernd, Hongo, Seiji, Höper, Dirk, Horie, Masayuki, Hughes, Holly R., Hyndman, Timothy, Jambai, Amara, Jardim, Rodrigo, Jiāng, Dàohóng, Jin, Qi, Jonson, Gilda B., Junglen, Sandra, Karadağ, Serpil, Keller, Karen E., Klempa, B., Klingström, Jonas, Kobinger, Gary, Kondō, Hideki, Koonin, Eugene V., Krupovic, Mart, Kurath, Gael, Kuzmin, Ivan V., Laenen, Lies, Lamb, Robert A., Lambert, Amy J., Langevin, Stanley L., Lee, Benhur, Lemos, Elba R.S., Leroy, Eric M., Li, Dexin, Li, Jianrong, Liang, Mifang, Liú, Wénwén, Liu, Yang, Lukashevich, Igor S., Maes, Piet, Marciel de Souza, William, Marklewitz, Marco, Marshall, Sergio H., Martelli, Giovanni P, Martin, Robert R., Marzano, Shin-Yi L., Massart, Sebastien, McCauley, John W., Mielke-Ehret, Nicole, Minafra, Angelantonio, Minutolo, Maria, Mirazimi, Ali, Mühlbach, Hans-Peter, Mühlberger, Elke, Naidu, Rayapati, Natsuaki, Tomohide, Navarro, Beatriz, Navarro, José A., Netesov, Sergey V., Neumann, Gabriele, Nowotny, N., Nunes, Márcio R.T., Nylund, Are, Okland, Arnfinn Lodden, Oliveira, Renata C., Palacios, Gustavo, Pallás, Vicente, Pályi, Bernadett, Papa, Anna, Parrish, Colin R., Pauvolid-Corrêa, Alex, Pawęska, Janusz T., Payne, Susan, Pérez, Daniel R., Pfaff, Florian, Radoshitzky, Sheli R., Rahman, Aziz-Ul, Ramos-González, Pedro L., Resende, Renato O., Reyes, Carina A., Rima, Bertus K., Romanowski, Víctor, Robles Luna, Gabriel, Rota, Paul, Rubbenstroth, Dennis, Runstadler, Jonathan A., Ruzek, Daniel, Sabanadzovic, Sead, Salát, Jiří, Sall, Amadou Alpha, Salvato, Maria S., Sarpkaya, Kamil, Sasaya, Takahide, Schwemmle, Martin, Shabbir, Muhammad Z., Shí, Xiǎohóng, Shí, Zhènglì, Shirako, Yukio, Simmonds, Peter, Širmarová, Jana, Sironi, Manuela, Smither, Sophie, Smura, Teemu, Song, Jin-Won, Spann, Kirsten, Spengler, Jessica R., Stenglein, Mark D., Stone, David M., Straková, Petra, Takada, Ayato, Tesh, Robert B., Thornburg, Natalie J., Tomonaga, Keizō, Tordo, Noël, Towner, Jonathan S., Turina, Massimo, Tzanetakis, Ioannis E., Ulrich, R. G., Vaira, Anna Maria, Van den Hoogen, Bernadette, Varsani, Arvind, Vasilakis, Nikos, Verbeek, Martin, Wahl, Victoria, Walker, Peter J., Wang, Hui, Wang, Jianwei, Wang, Xifeng, Wang, Lin-Fa, Wèi, Tàiyún, Wells, Heather, Whitfield, Anna E., Williams, John V., Wolf, Yuri I., Wú, Zhìqiáng, Yang, Xin, Yáng, Xīnglóu, Yu, Xuejie, Yutin, Natalya, Zerbini, F. Murilo, Zhang, Tong, Zhang, Yong-Zhen, Zhou, Guohui, Zhou, Xueping, National Institute of Allergy and Infectious Diseases (US), National Cancer Institute (US), National Institutes of Health (US), Frederick National Laboratory for Cancer Research (US), US Department of Homeland Security, National Institute of Food and Agriculture (US), Kuhn, Jens H. [0000-0002-7800-6045], Adkins, Scott [0000-0003-0095-8414], Alioto, Daniela [0000-0002-4954-8363], Alkhovsky, Sergey V. [0000-0001-6913-5841], Amarasinghe, Gaya K. [0000-0002-0418-9707], Avsic-Zupanc, Tatjana [0000-0001-6243-0688], Ayllón, María A. [0000-0001-7893-6106], Bahl, Justin [0000-0001-7572-4300], Balkema-Buschmann, A. [0000-0001-7613-9592], Ballinger, Matthew J. [0000-0001-7453-8725], Bartonička, Tomáš [0000-0001-7335-2435], Basler, Christopher F. [0000-0003-4195-425X], Bavari, Sina [0000-0001-8424-5635], Beer, Martin [0000-0002-0598-5254], Bente, Dennis A. [0000-0002-5150-7368], Bergeron, Éric [0000-0003-3398-8628], Bird, Brian H. [0000-0001-8170-8710], Blair, Carol D. [0000-0002-2803-0354], Blasdell, Kim R. [0000-0003-2121-0376], Bradfute, Steven B. [0000-0002-1985-751X], Breyta, Rachel [0000-0002-9106-1014], Briese, Thomas [0000-0002-4819-8963], Brown, Paul A. [0000-0002-6697-7688], Buchholz, Ursula J. [0000-0002-2329-3198], Buchmeier, Michael J. [0000-0002-2387-9287], Bukreyev, Alexander [0000-0002-0342-4824], Burt, Felicity [0000-0002-7238-7799], Buzkan, Nihal [0000-0002-0428-0447], Calisher, Charles H. [0000-0003-0213-294X], Cao, Mengji [0000-0003-0396-262X], Casas, Inmaculada [0000-0003-1840-1198], Chamberlain, John [0000-0002-7387-6420], Chandran, Kartik [0000-0003-0232-7077], Charrel, Rémi N. [0000-0002-7675-8251], Chen, Biao [0000-0002-2450-9296], Chiumenti, Michela [0000-0002-8412-3037], Choi, Il-Ryong [0000-0002-8035-7573], Clegg, J Christopher S. [0000-0003-3765-1862], Crozier, Ian [0000-0003-2485-4011], da Graça, John V. [0000-0003-0743-1519], Dávila, Alberto M.R. [0000-0002-6918-7673], de la Torre, J. C. [0000-0002-8171-8115], de Lamballerie, Xavier [0000-0001-7895-2720], De Swart, Rik L. [0000-0003-3599-8969], Di Bello, Patrick L. [0000-0002-4773-8040], Di Paola, Nicholas [0000-0002-9694-3913], Di Serio, Francesco [0000-0003-2822-704X], Dietzgen, Ralf G. [0000-0002-7772-2250], Digiaro, Michele [0009-0006-3089-3606], Dolja, Valerian V. [0000-0002-8148-4670], Dolnik, Olga [0000-0001-7739-4798], Drexler, J. Felix [0000-0002-3509-0232], Dürrwald, Ralf [0000-0002-3432-0438], Dufkova, Lucie [0000-0001-7302-2057], Dundon, William G. [0000-0002-2776-169X], Duprex, W. Paul [0000-0003-1716-6376], Dye, John M. [0000-0002-0883-5016], Easton, Andrew J. [0000-0002-2288-3882], Ebihara, Hideki [0000-0002-2576-9735], Elbeaino, Toufic [0000-0003-2211-7907], Ergünay, Koray [0000-0001-5422-1982], Fernandes, Jorlan [0000-0002-5039-0604], Fooks, Anthony R. [0000-0002-3243-6154], Formenty, Pierre B.H. [0000-0002-9482-5411], Forth, Leonie F [0000-0002-2708-2515], Fouchier, Ron A.M. [0000-0001-8095-2869], Freitas-Astúa, Juliana [0000-0002-0506-6880], Gago-Zachert, Selma [0000-0002-1084-2119], Gāo, George Fú [0000-0002-3869-615X], García, María Laura [0000-0001-6468-6943], García-Sastre, Adolfo [0000-0002-6551-1827], Garrison, Aura R. [0000-0003-3034-6400], Gbakima, Aiah [0000-0002-7642-0752], Goldstein, Tracey [0000-0002-1672-7410], Gonzalez, Jean-Paul J. [0000-0003-3063-1770], Griffiths, Anthony [0000-0001-5435-8364], Groschup, M. H. [0000-0003-0215-185X], Günther, Stephan [0000-0002-6562-0230], Guterres, Alexandro [0000-0001-8323-1477], Hall, Roy A. [0000-0001-5778-1387], Hammond, John [0000-0001-7593-747X], Hassan, Mohamed [0000-0002-1289-0878], Hepojoki, Jussi [0000-0001-5699-214X], Hepojoki, Satu [0000-0002-0696-1879], Hetzel, Udo [0000-0001-9142-560X], Hewson, Roger [0000-0003-2273-3152], Höper, Dirk [0000-0001-8408-2274], Horie, Masayuki [0000-0003-4682-7698], Hyndman, Timothy [0000-0002-7047-5023], Hughes, Holly R. [0000-0003-1380-8263], Hyndman, Timothy [0000-0003-4083-562X], Jambai, Amara [0000-0003-3754-2500], Jardim, Rodrigo [0000-0002-0943-5356], Jiāng, Dàohóng [0000-0002-3862-7461], Jonson, Gilda B. [0000-0003-0097-8634], Junglen, Sandra [0000-0002-3799-6011], Klempa, B. [0000-0002-6931-1224], Klingström, Jonas [0000-0001-9076-1441], Kobinger, Gary [0000-0003-0612-2298], Kondō, Hideki [0000-0001-9220-5350], Koonin, Eugene V. [0000-0003-3943-8299], Krupovic, Mart [0000-0001-5486-0098], Kurath, Gael [0000-0003-3294-560X], Laenen, Lies [0000-0001-9118-8608], Langevin, Stanley L. [0000-0002-6833-271X], Lee, Benhur [0000-0003-0760-1709], Lemos, Elba R.S. [0000-0003-3761-0200], Lukashevich, Igor S. [0000-0001-6523-5116], Maes, Piet [0000-0002-4571-5232], Marklewitz, Marco [0000-0003-1828-8770], Marzano, Shin-Yi L. [0000-0003-0548-3761], Mielke-Ehret, Nicole [0000-0003-0096-0696], Minafra, Angelantonio [0000-0002-0547-7129], Minutolo, Maria [0000-0001-7816-2657], Mühlberger, Elke [0000-0003-3547-9376], Naidu, Rayapati [0000-0002-7273-5116], Natsuaki, Tomohide [0000-0003-1823-7308], Navarro, José A. [0000-0002-0536-6074], Netesov, Sergey V. [0000-0002-7786-2464], Neumann, Gabriele [0000-0001-7054-1775], Nowotny, N. [0000-0002-3548-571X], Nunes, Márcio R.T. [0000-0003-0529-0230], Nylund, Are [0000-0002-1932-6604], Okland, Arnfinn Lodden [0000-0003-3062-4386], Oliveira, Renata C. [0000-0002-1904-7533], Pallás, Vicente [0000-0003-4954-989X], Pályi, Bernadett [0000-0003-1975-4198], Parrish, Colin R. [0000-0002-1836-6655], Pauvolid-Corrêa, Alex [0000-0002-6924-157X], Pawęska, Janusz T. [0000-0001-8776-7519], Radoshitzky, Sheli R. [0000-0001-8976-8056], Rahman, Aziz-Ul [0000-0002-3342-4462], Ramos-González, Pedro L. [0000-0002-9640-6587], Resende, Renato O. [0000-0003-3852-1576], Romanowski, Víctor [0000-0001-6378-7929], Robles Luna, Gabriel [0000-0003-3409-5557], Rota, Paul [0000-0002-8595-4094], Rubbenstroth, Dennis [0000-0002-8209-6274], Runstadler, Jonathan A. [0000-0002-6747-7765], Ruzek, Daniel [0000-0003-4655-2380], Sabanadzovic, Sead [0000-0002-2995-2633], Salát, Jiří [0000-0002-9915-8953], Sarpkaya, Kamil [0000-0001-5794-668X], Sasaya, Takahide [0000-0002-5020-9377], Shabbir, Muhammad Z. [0000-0003-4908-3313], Shí, Zhènglì [0000-0002-7309-6838], Sironi, Manuela [0000-0002-2267-5266], Smither, Sophie [0000-0002-7835-3581], Smura, Teemu [0000-0002-9187-3151], Spann, Kirsten [0000-0003-0567-8382], Spengler, Jessica R. [0000-0002-5383-0513], Stenglein, Mark D. [0000-0002-0993-813X], Takada, Ayato [0000-0003-2464-6642], Tesh, Robert B. [0000-0002-9226-397X], Thornburg, Natalie J. [0000-0003-3523-3616], Tomonaga, Keizō [0000-0003-0405-7103], Tordo, Noël [0000-0001-5873-059X], Towner, Jonathan S. [0000-0002-6473-3049], Turina, Massimo [0000-0002-9659-9470], Tzanetakis, Ioannis E. [0000-0002-5970-1763], Ulrich, R. G. [0000-0002-5620-1528], Vaira, Anna Maria [0000-0003-2526-4419], Van den Hoogen, Bernadette [0000-0003-1996-8559], Varsani, Arvind [0000-0003-4111-2415], Verbeek, Martin [0000-0002-8973-3803], Wahl, Victoria [0000-0002-6588-4308], Whitfield, Anna E. [0000-0002-3538-015X], Wolf, Yuri I. [0000-0002-0247-8708], Yutin, Natalya [0000-0002-3633-5123], Zerbini, F. Murilo [0000-0001-8617-0200], Kuhn, Jens H., Adkins, Scott, Alioto, Daniela, Alkhovsky, Sergey V., Amarasinghe, Gaya K., Anthony, Simon J., Avsic-Zupanc, Tatjana, Ayllón, María A., Bahl, Justin, Balkema-Buschmann, A., Ballinger, Matthew J., Bartonička, Tomáš, Basler, Christopher F., Bavari, Sina, Beer, Martin, Bente, Dennis A., Bergeron, Éric, Bird, Brian H., Blair, Carol D., Blasdell, Kim R., Bradfute, Steven B., Breyta, Rachel, Briese, Thomas, Brown, Paul A., Buchholz, Ursula J., Buchmeier, Michael J., Bukreyev, Alexander, Burt, Felicity, Buzkan, Nihal, Calisher, Charles H., Cao, Mengji, Casas, Inmaculada, Chamberlain, John, Chandran, Kartik, Charrel, Rémi N., Chen, Biao, Chiumenti, Michela, Choi, Il-Ryong, Clegg, J Christopher S., Crozier, Ian, da Graça, John V., Dal Bó, Elena, Dávila, Alberto M.R., de la Torre, J. C., de Lamballerie, Xavier, De Swart, Rik L., Di Bello, Patrick L., Di Paola, Nicholas, Di Serio, Francesco, Dietzgen, Ralf G., Digiaro, Michele, Dolja, Valerian V., Dolnik, Olga, Drebot, Michael A., Drexler, J. Felix, Dürrwald, Ralf, Dufkova, Lucie, Dundon, William G., Duprex, W. Paul, Dye, John M., Easton, Andrew J., Ebihara, Hideki, Elbeaino, Toufic, Ergünay, Koray, Fernandes, Jorlan, Fooks, Anthony R., Formenty, Pierre B.H., Forth, Leonie F., Fouchier, Ron A.M., Freitas-Astúa, Juliana, Gago-Zachert, Selma, Gāo, George Fú, García, María Laura, García-Sastre, Adolfo, Garrison, Aura R., Gbakima, Aiah, Goldstein, Tracey, Gonzalez, Jean-Paul J., Griffiths, Anthony, Groschup, M. H., Günther, Stephan, Guterres, Alexandro, Hall, Roy A., Hammond, John, Hassan, Mohamed, Hepojoki, Jussi, Hepojoki, Satu, Hetzel, Udo, Hewson, Roger, Hoffmann, Bernd, Hongo, Seiji, Höper, Dirk, Horie, Masayuki, Hughes, Holly R., Hyndman, Timothy, Jambai, Amara, Jardim, Rodrigo, Jiāng, Dàohóng, Jin, Qi, Jonson, Gilda B., Junglen, Sandra, Karadağ, Serpil, Keller, Karen E., Klempa, B., Klingström, Jonas, Kobinger, Gary, Kondō, Hideki, Koonin, Eugene V., Krupovic, Mart, Kurath, Gael, Kuzmin, Ivan V., Laenen, Lies, Lamb, Robert A., Lambert, Amy J., Langevin, Stanley L., Lee, Benhur, Lemos, Elba R.S., Leroy, Eric M., Li, Dexin, Li, Jianrong, Liang, Mifang, Liú, Wénwén, Liu, Yang, Lukashevich, Igor S., Maes, Piet, Marciel de Souza, William, Marklewitz, Marco, Marshall, Sergio H., Martelli, Giovanni P, Martin, Robert R., Marzano, Shin-Yi L., Massart, Sebastien, McCauley, John W., Mielke-Ehret, Nicole, Minafra, Angelantonio, Minutolo, Maria, Mirazimi, Ali, Mühlbach, Hans-Peter, Mühlberger, Elke, Naidu, Rayapati, Natsuaki, Tomohide, Navarro, Beatriz, Navarro, José A., Netesov, Sergey V., Neumann, Gabriele, Nowotny, N., Nunes, Márcio R.T., Nylund, Are, Okland, Arnfinn Lodden, Oliveira, Renata C., Palacios, Gustavo, Pallás, Vicente, Pályi, Bernadett, Papa, Anna, Parrish, Colin R., Pauvolid-Corrêa, Alex, Pawęska, Janusz T., Payne, Susan, Pérez, Daniel R., Pfaff, Florian, Radoshitzky, Sheli R., Rahman, Aziz-Ul, Ramos-González, Pedro L., Resende, Renato O., Reyes, Carina A., Rima, Bertus K., Romanowski, Víctor, Robles Luna, Gabriel, Rota, Paul, Rubbenstroth, Dennis, Runstadler, Jonathan A., Ruzek, Daniel, Sabanadzovic, Sead, Salát, Jiří, Sall, Amadou Alpha, Salvato, Maria S., Sarpkaya, Kamil, Sasaya, Takahide, Schwemmle, Martin, Shabbir, Muhammad Z., Shí, Xiǎohóng, Shí, Zhènglì, Shirako, Yukio, Simmonds, Peter, Širmarová, Jana, Sironi, Manuela, Smither, Sophie, Smura, Teemu, Song, Jin-Won, Spann, Kirsten, Spengler, Jessica R., Stenglein, Mark D., Stone, David M., Straková, Petra, Takada, Ayato, Tesh, Robert B., Thornburg, Natalie J., Tomonaga, Keizō, Tordo, Noël, Towner, Jonathan S., Turina, Massimo, Tzanetakis, Ioannis E., Ulrich, R. G., Vaira, Anna Maria, Van den Hoogen, Bernadette, Varsani, Arvind, Vasilakis, Nikos, Verbeek, Martin, Wahl, Victoria, Walker, Peter J., Wang, Hui, Wang, Jianwei, Wang, Xifeng, Wang, Lin-Fa, Wèi, Tàiyún, Wells, Heather, Whitfield, Anna E., Williams, John V., Wolf, Yuri I., Wú, Zhìqiáng, Yang, Xin, Yáng, Xīnglóu, Yu, Xuejie, Yutin, Natalya, Zerbini, F. Murilo, Zhang, Tong, Zhang, Yong-Zhen, Zhou, Guohui, and Zhou, Xueping
Abstract: In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
Published: 2020

33. What is needed to achieve HCV microelimination among HIV-infected populations in Andalusia, Spain: a modeling analysis

Author: Gilead Sciences, National Institute on Drug Abuse (US), Center for AIDS Research (US), National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Instituto Nacional del Cáncer (España), National Institute of Mental Health (US), Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Heart, Lung, and Blood Institute (US), National Institute of Diabetes and Digestive and Kidney Diseases (US), Ministerio de Sanidad y Seguridad Social (España), European Commission, Instituto de Salud Carlos III, Fundación para la Investigación en Salud, Red Española de Investigación en SIDA, Skaathun, Britt, Borquez, Annick, Rivero-Juárez, Antonio, Mehta, Sanjay R., Téllez, Francisco, Castaño‐Carracedo, M., Merino, Dolores, Palacios, Rosario, Macías Sánchez, Juan, Rivero, Antonio, Martin, Natasha K., Gilead Sciences, National Institute on Drug Abuse (US), Center for AIDS Research (US), National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Instituto Nacional del Cáncer (España), National Institute of Mental Health (US), Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Heart, Lung, and Blood Institute (US), National Institute of Diabetes and Digestive and Kidney Diseases (US), Ministerio de Sanidad y Seguridad Social (España), European Commission, Instituto de Salud Carlos III, Fundación para la Investigación en Salud, Red Española de Investigación en SIDA, Skaathun, Britt, Borquez, Annick, Rivero-Juárez, Antonio, Mehta, Sanjay R., Téllez, Francisco, Castaño‐Carracedo, M., Merino, Dolores, Palacios, Rosario, Macías Sánchez, Juan, Rivero, Antonio, and Martin, Natasha K.
Abstract: [Background] Scale-up of hepatitis C virus (HCV) treatment for HIV/HCV coinfected individuals is occurring in Spain, the vast majority (> 85%) with a reported history of injecting drug use and a smaller population of co-infected men who have sex with men (MSM). We assess impact of recent treatment scale-up to people living with HIV (PLWH) and implications for achieving the WHO HCV incidence elimination target (80% reduction 2015–2030) among PLWH and overall in Andalusia, Spain, using dynamic modeling., [Methods] A dynamic transmission model of HCV/HIV coinfection was developed. The model was stratified by people who inject drugs (PWID) and MSM. The PWID component included dynamic HCV transmission from the HCV-monoinfected population. The model was calibrated to Andalusia based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals representing > 99% coinfected individuals in care in Andalusia). From HERACLES, we incorporated HCV treatment among diagnosed PLWH of 10.5%/year from 2004 to 2014, and DAAs at 33%/year from 2015 with 94.8% SVR. We project the impact of current and scaled-up HCV treatment for PLWH on HCV prevalence and incidence among PLWH and overall., [Results] Current treatment rates among PLWH (scaled-up since 2015) could substantially reduce the number of diagnosed coinfected individuals (mean 76% relative reduction from 2015 to 2030), but have little impact on new diagnosed coinfections (12% relative reduction). However, DAA scale-up to PWLH in 2015 would have minimal future impact on new diagnosed coinfections (mean 9% relative decrease from 2015 to 2030). Similarly, new cases of HCV would only reduce by a mean relative 29% among all PWID and MSM due to ongoing infection/reinfection. Diagnosing/treating all PLWH annually from 2020 would increase the number of new HCV infections among PWLH by 28% and reduce the number of new HCV infections by 39% among the broader population by 2030., [Conclusion] Targeted scale-up of HCV treatment to PLWH can dramatically reduce prevalence among this group but will likely have little impact on the annual number of newly diagnosed HIV/HCV coinfections. HCV microelimination efforts among PWLH in Andalusia and settings where a large proportion of PLWH have a history of injecting drug use will require scaled-up HCV diagnosis and treatment among PLWH and the broader population at risk.
Published: 2020

34. Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients

Author: Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Red Española de Investigación en Patología Infecciosa, National Institute of Allergy and Infectious Diseases (US), Centers of Excellence for Influenza Research and Surveillance (US), Aydillo, T. A., Escalera, Alba, Strohmeier, Shirin, Aslam, Sadaf, Sánchez-Céspedes, Javier, Ayllón, Juan, Roca-Oporto, Cristina, Pérez-Romero, Pilar, Montejo, Miguel, Gavaldà, Joan, Muñoz, Patricia, López-Medrano, Francisco, Carratalà, Jordi, Krammer, Florian, García-Sastre, Adolfo, Cordero-Matía, Elisa, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Red Española de Investigación en Patología Infecciosa, National Institute of Allergy and Infectious Diseases (US), Centers of Excellence for Influenza Research and Surveillance (US), Aydillo, T. A., Escalera, Alba, Strohmeier, Shirin, Aslam, Sadaf, Sánchez-Céspedes, Javier, Ayllón, Juan, Roca-Oporto, Cristina, Pérez-Romero, Pilar, Montejo, Miguel, Gavaldà, Joan, Muñoz, Patricia, López-Medrano, Francisco, Carratalà, Jordi, Krammer, Florian, García-Sastre, Adolfo, and Cordero-Matía, Elisa
Abstract: Hemagglutination-inhibitory antibodies are usually highly strain specific with little effect on infection with drifted or shifted strains. The significance of broadly cross-reactive non-HAI anti-influenza antibodies against conserved domains of virus glycoproteins, such as the hemagglutinin (HA) stalk, is of great interest. We characterize a cohort of 40 H1N1pmd09 influenza-infected patients and identify lower respiratory symptoms (LRSs) as a predictor for development of pneumonia. A binomial logistic regression of log10 pre-existing antibody values shows that the probability of LRS occurrence decreased with increased anti-HA full-length and stalk antibody ELISA titers. However, a multilevel logistic regression model adjusted by other potential serocorrelates demonstrates that only antibodies directed against the stalk of HA correlate with protection from lower respiratory infection, limiting disease progression. Our predictive model indicates that a threshold of protective immunity based on broadly cross-reactive HA stalk antibodies could be feasible.
Published: 2020

35. Vimentin as a multifaceted player and potential therapeutic target in viral infections

Author: Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, National Institute of Allergy and Infectious Diseases (US), Ramos, Irene [0000-0002-0223-0120], Stamatakis, Konstantinos [0000-0001-9934-3502], Oeste, Clara L. [0000-0002-7035-132X], Pérez-Sala, Dolores [0000-0003-0600-665X], Ramos, Irene, Stamatakis, Konstantinos, Oeste, Clara L., Pérez-Sala, Dolores, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, National Institute of Allergy and Infectious Diseases (US), Ramos, Irene [0000-0002-0223-0120], Stamatakis, Konstantinos [0000-0001-9934-3502], Oeste, Clara L. [0000-0002-7035-132X], Pérez-Sala, Dolores [0000-0003-0600-665X], Ramos, Irene, Stamatakis, Konstantinos, Oeste, Clara L., and Pérez-Sala, Dolores
Abstract: Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed.
Published: 2020

36. In vivo rescue of recombinant Zika virus from an infectious cDNA clone and its implications in vaccine development

Author: Ministerio de Economía y Competitividad (España), National Institutes of Health (US), University of Georgia Research Foundation, National Institute of Allergy and Infectious Diseases (US), Ávila-Pérez, Ginés, Nogales, Aitor, Park, Jun-Gyu, Morales Vasquez, Desarey, Dean, David A., Barravecchia, Michael, Pérez, Daniel R., Almazán, Fernando, Martínez-Sobrido, Luis, Ministerio de Economía y Competitividad (España), National Institutes of Health (US), University of Georgia Research Foundation, National Institute of Allergy and Infectious Diseases (US), Ávila-Pérez, Ginés, Nogales, Aitor, Park, Jun-Gyu, Morales Vasquez, Desarey, Dean, David A., Barravecchia, Michael, Pérez, Daniel R., Almazán, Fernando, and Martínez-Sobrido, Luis
Abstract: Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that has been known to circulate for decades causing mild febrile illness. The more recent ZIKV outbreaks in the Americas and the Caribbean associated with congenital malformations and Guillain-Barré syndrome in adults have placed public health officials in high alert and highlight the significant impact of ZIKV on human health. New technologies to study the biology of ZIKV and to develop more effective prevention options are highly desired. In this study we demonstrate that direct delivery in mice of an infectious ZIKV cDNA clone allows the rescue of recombinant (r)ZIKV in vivo. A bacterial artificial chromosome containing the sequence of ZIKV strain Paraiba/2015 under the control of the cytomegalovirus promoter was complexed with a commercial transfection reagent and administrated using different routes in type-I interferon receptor deficient A129 mice. Clinical signs and death associated with ZIKV viremia were observed in mice. The rZIKV recovered from these mice remained fully virulent in a second passage in mice. Interestingly, infectious rZIKV was also recovered after intraperitoneal inoculation of the rZIKV cDNA in the absence of transfection reagent. Further expanding these studies, we demonstrate that a single intraperitoneal inoculation of a cDNA clone encoding an attenuated rZIKV was safe, highly immunogenic, and provided full protection against lethal ZIKV challenge. This novel in vivo reverse genetics method is a potentially suitable delivery platform for the study of wild-type and live-attenuated ZIKV devoid of confounding factors typical associated with in vitro systems. Moreover, our results open the possibility of employing similar in vivo reverse genetic approaches for the generation of other viruses and, therefore, change the way we will use reverse genetics in the future.
Published: 2020

37. High-depth African genomes inform human migration and health

Author: National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Wellcome Trust, Generalitat de Catalunya, Ministerio de Economía y Competitividad (España), Choudhury, Ananyo, Aron, Shaun, Botigué, Laura R., Sengupta, Dhriti, Botha, Gerrit, Bensellak, Taoufik, Wells, Gordon, Kumuthini, Judit, Shriner, Daniel, Fakim, Yasmina J., Ghoorah, Anisah W., Dareng, Eileen, Odia, Trust, Falola, Oluwadamilare, Adebiyi, Ezekiel, Hazelhurst, Scott, Mazandu, Gaston, Nyangiri, Oscar A., Mbiyavanga, Mamana, Benkahla, Alia, Kassim, Samar K., Mulder, Nicola, Adebamowo, Sally N., Chimusa, Emile R., Muzny, Donna, Metcalf, Ginger, Gibbs, Richard A., Rotimi, Charles, Ramsay, Michèle, Adeyemo, Adebowale A., Lombard, Zané, Hanchard, Neil A., National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Wellcome Trust, Generalitat de Catalunya, Ministerio de Economía y Competitividad (España), Choudhury, Ananyo, Aron, Shaun, Botigué, Laura R., Sengupta, Dhriti, Botha, Gerrit, Bensellak, Taoufik, Wells, Gordon, Kumuthini, Judit, Shriner, Daniel, Fakim, Yasmina J., Ghoorah, Anisah W., Dareng, Eileen, Odia, Trust, Falola, Oluwadamilare, Adebiyi, Ezekiel, Hazelhurst, Scott, Mazandu, Gaston, Nyangiri, Oscar A., Mbiyavanga, Mamana, Benkahla, Alia, Kassim, Samar K., Mulder, Nicola, Adebamowo, Sally N., Chimusa, Emile R., Muzny, Donna, Metcalf, Ginger, Gibbs, Richard A., Rotimi, Charles, Ramsay, Michèle, Adeyemo, Adebowale A., Lombard, Zané, and Hanchard, Neil A.
Abstract: The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health.
Published: 2020

38. AGL2017-82570-RReverse genetics approaches for the development of new vaccines against influenza A virus infections

Author: National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Martínez-Sobrido, Luis, DeDiego, Marta L., Nogales, Aitor, National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Martínez-Sobrido, Luis, DeDiego, Marta L., and Nogales, Aitor
Abstract: Influenza A viruses (IAVs) represent a serious concern globally because they are capable of rapid spread and cause severe disease in humans and other animals. The development and implementation of plasmid-based reverse genetics approaches have allowed the manipulation and recovery of recombinant IAVs from complementary DNA copies of the viral genome. Furthermore, IAV reverse genetics have provided researchers an efficient and powerful platform to introduce specific changes in the viral genome with the final goal of studying IAV biology, designing more effective vaccine strategies, and to reduce the rates of incidence and mortality associated with viral infections. In this review, we briefly discuss IAV reverse genetics and their applications to prevent IAV infections.
Published: 2020

39. Editorial: Atypical Functions of Leukocyte Chemoattractant Receptors

Author: Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Helmut Horten Foundation, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Swiss National Science Foundation, Rodríguez-Fernández, José Luis, Mellado, Mario, Thelen, Marcus, Murphy, Philip M., Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Helmut Horten Foundation, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Swiss National Science Foundation, Rodríguez-Fernández, José Luis, Mellado, Mario, Thelen, Marcus, and Murphy, Philip M.
Abstract: Chemoattraction is a process that involves directed cell movement toward extracellular chemical stimuli. It is a fundamental feature of all biological systems that was discovered in the late nineteenth century, when the word “chemotaxis” was coined by the German biologist Wilhelm Pfeffer. Metchnikoff’s 1882 description of macrophages from starfish larvae migrating toward an implanted rose thorn irritant represents a seminal observation of chemoattraction in vivo. Since then immunologists have described many chemoattractants, including nucleotides, adenosine, lipids (e.g., leukotrienes, prostaglandins, and platelet-activating factor), proteolytic fragments of complement proteins (e.g., C3a and C5a), small peptides (e.g., N-formyl peptides), and small proteins (e.g., chemokines, non-chemokine cytokines, and defensins). Chemokines comprise the largest known group of chemoattractants (1, 2).
Published: 2020

40. Medicinal Chemistry Optimization of a Diaminopurine Chemotype: Toward a Lead for Trypanosoma brucei Inhibitors

Author: Tres Cantos Open Lab Foundation, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Singh, Baljinder, Díaz-González, Rosario, Ceballos-Pérez, Gloria, Rojas-Barros, Domingo I., Gunaganti, Naresh, Gillingwater, Kirsten, Santos Martinez-Martinez, María, Manzano, Pilar, Navarro, M., Pollastri, M.P., Tres Cantos Open Lab Foundation, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Singh, Baljinder, Díaz-González, Rosario, Ceballos-Pérez, Gloria, Rojas-Barros, Domingo I., Gunaganti, Naresh, Gillingwater, Kirsten, Santos Martinez-Martinez, María, Manzano, Pilar, Navarro, M., and Pollastri, M.P.
Abstract: Human African trypanosomiasis (HAT), or sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei and transmitted through the bite of infected tsetse flies. The disease is considered fatal if left untreated. To identify new chemotypes against Trypanosoma brucei, previously we identified 797 potent kinase-targeting inhibitors grouped into 59 clusters plus 53 singleton compounds with at least 100-fold selectivity over HepG2 cells. From this set of hits, a cluster of diaminopurine-derived compounds was identified. Herein, we report our medicinal chemistry investigation involving the exploration of structure¿activity and structure¿property relationships around one of the high-throughput screening (HTS) hits, N2-(thiophen-3-yl)-N6-(2,2,2-trifluoroethyl)-9H-purine-2,6-diamine (1, NEU-1106). This work led to the identification of a potent lead compound (4aa, NEU-4854) with improved in vitro absorption, distribution, metabolism, and excretion (ADME) properties, which was progressed into proof-of-concept translation of in vitro antiparasitic activity to in vivo efficacy.
Published: 2020

41. Nanotechnology Responses to COVID‐19

Author: Ministerio de Economía y Competitividad (España), European Commission, National Institute of Allergy and Infectious Diseases (US), Ruiz-Hitzky, Eduardo, Darder, Margarita, Wicklein, Bernd, Ruiz‐Garcia, Cristina, Martín‐Sampedro, Raquel, Real, Gustavo del, Aranda, Pilar, Ministerio de Economía y Competitividad (España), European Commission, National Institute of Allergy and Infectious Diseases (US), Ruiz-Hitzky, Eduardo, Darder, Margarita, Wicklein, Bernd, Ruiz‐Garcia, Cristina, Martín‐Sampedro, Raquel, Real, Gustavo del, and Aranda, Pilar
Abstract: Researchers, engineers, and medical doctors are made aware of the severity of the COVID‐19 infection and act quickly against the coronavirus SARS‐CoV‐2 using a large variety of tools. In this review, a panoply of nanoscience and nanotechnology approaches show how these disciplines can help the medical, technical, and scientific communities to fight the pandemic, highlighting the development of nanomaterials for detection, sanitation, therapies, and vaccines. SARS‐CoV‐2, which can be regarded as a functional core–shell nanoparticle (NP), can interact with diverse materials in its vicinity and remains attached for variable times while preserving its bioactivity. These studies are critical for the appropriate use of controlled disinfection systems. Other nanotechnological approaches are also decisive for the development of improved novel testing and diagnosis kits of coronavirus that are urgently required. Therapeutics are based on nanotechnology strategies as well and focus on antiviral drug design and on new nanoarchitectured vaccines. A brief overview on patented work is presented that emphasizes nanotechnology applied to coronaviruses. Finally, some comments are made on patents of the initial technological responses to COVID‐19 that have already been put in practice.
Published: 2020

42. Target product profile for a test for the early assessment of treatment efficacy in chagas disease patients: An expert consensus

Author: Generalitat de Catalunya, Instituto de Salud Carlos III, National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Ministerio de Economía y Competitividad (España), Ministero della Salute, Alonso-Padillaid, J., Abril, M., de Noya, B.A., Almeida, Igor C., Angheben, A., Jorge, T.A., Chatelain, E., Esteva, Monica, Gascón, Joaquim, Grijalva, M.J., Guhl, F., Hasslochermoreno, A.M., López López, Manuel Carlos, Luquetti, A., Noya, O., Pinazo, M.J., Ramsey, J.M., Ribeiro, I., Ruiz, A.M., Schijman, A.G., Sosa-Estani, S., Thomas, María del Carmen, M., Torrico, F., Zreinid, M., Picado, A., Generalitat de Catalunya, Instituto de Salud Carlos III, National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Ministerio de Economía y Competitividad (España), Ministero della Salute, Alonso-Padillaid, J., Abril, M., de Noya, B.A., Almeida, Igor C., Angheben, A., Jorge, T.A., Chatelain, E., Esteva, Monica, Gascón, Joaquim, Grijalva, M.J., Guhl, F., Hasslochermoreno, A.M., López López, Manuel Carlos, Luquetti, A., Noya, O., Pinazo, M.J., Ramsey, J.M., Ribeiro, I., Ruiz, A.M., Schijman, A.G., Sosa-Estani, S., Thomas, María del Carmen, M., Torrico, F., Zreinid, M., and Picado, A.
Abstract: descripción no proporcionada por scopus
Published: 2020

43. Risk and management of patients with mastocytosis and MCAS in the SARS-CoV-2 (COVID-19) pandemic: Expert opinions

Author: Austrian Science Fund, Charles and Ann Johnson Foundation, National Institute of Allergy and Infectious Diseases (US), Valent, Peter, Akin, Cem, Bonadonna, Patrizia, Brockow, Knut, Niedoszytko, Marek, Nedoszytko, Boguslaw, Butterfield, Joseph H., Álvarez-Twose, Iván, Sotlar, Karl, Schwaab, Juliana, Jawhar, Mohamad, Reiter, Andreas, Castells, Mariana, Sperr, Wolfgang R., Kluin-Nelemans, Hanneke C., Hermine, Olivier, Gotlib, Jason, Zanotti, Roberta, Broesby-Olsen, Sigurd, Horny, Hans-Peter, Triggiani, Massimo, Siebenhaar, Frank, Orfao, Alberto, Metcalfe, Dean D., Arock, Michel, Hartmann, Karin, Austrian Science Fund, Charles and Ann Johnson Foundation, National Institute of Allergy and Infectious Diseases (US), Valent, Peter, Akin, Cem, Bonadonna, Patrizia, Brockow, Knut, Niedoszytko, Marek, Nedoszytko, Boguslaw, Butterfield, Joseph H., Álvarez-Twose, Iván, Sotlar, Karl, Schwaab, Juliana, Jawhar, Mohamad, Reiter, Andreas, Castells, Mariana, Sperr, Wolfgang R., Kluin-Nelemans, Hanneke C., Hermine, Olivier, Gotlib, Jason, Zanotti, Roberta, Broesby-Olsen, Sigurd, Horny, Hans-Peter, Triggiani, Massimo, Siebenhaar, Frank, Orfao, Alberto, Metcalfe, Dean D., Arock, Michel, and Hartmann, Karin
Abstract: The COVID-19 (SARS-CoV-2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase and patients at risk can only be protected to a degree, since the virulent state may be asymptomatic. Risk factors concerning COVID-19-induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here within, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. As no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Whereas the overall risk to acquire the SARS-CoV-2 virus may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain co-morbidities, mast cell activation-related events affecting the cardiovascular or bronchopulmonary system and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. By contrast, other therapies, such as anti-mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider.
Published: 2020

44. The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines

Author: National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Department of Agriculture (US), Canadian Institutes of Health Research, Ministerio de Economía y Competitividad (España), Marina, Alberto [0000-0002-1334-5273], Tiwari, Nitija, López-Redondo, Marisa, Miguel-Romero, Laura, Kulhankova, Katarina, Cahill, Michael P., Tran, Phuong M., Kinney, Kyle J., Kilgore, Samuel H., Al-Tameemi, Hassan, Herfst, Christine A., Tuffs, Stephen W., Kirby, John R., Boyd, Jeffery M., McCormick, John K., Salgado-Pabón, Wilmara, Marina, Alberto, Schlievert, Patrick M., Fuentes, Ernesto J., National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Department of Agriculture (US), Canadian Institutes of Health Research, Ministerio de Economía y Competitividad (España), Marina, Alberto [0000-0002-1334-5273], Tiwari, Nitija, López-Redondo, Marisa, Miguel-Romero, Laura, Kulhankova, Katarina, Cahill, Michael P., Tran, Phuong M., Kinney, Kyle J., Kilgore, Samuel H., Al-Tameemi, Hassan, Herfst, Christine A., Tuffs, Stephen W., Kirby, John R., Boyd, Jeffery M., McCormick, John K., Salgado-Pabón, Wilmara, Marina, Alberto, Schlievert, Patrick M., and Fuentes, Ernesto J.
Abstract: Staphylococcus aureus infections can lead to diseases that range from localized skin abscess to life-threatening toxic shock syndrome. The SrrAB two-component system (TCS) is a global regulator of S. aureus virulence and critical for survival under environmental conditions such as hypoxic, oxidative, and nitrosative stress found at sites of infection. Despite the critical role of SrrAB in S. aureus pathogenicity, the mechanism by which the SrrAB TCS senses and responds to these environmental signals remains unknown. Bioinformatics analysis showed that the SrrB histidine kinase contains several domains, including an extracellular Cache domain and a cytoplasmic HAMP-PAS-DHp-CA region. Here, we show that the PAS domain regulates both kinase and phosphatase enzyme activity of SrrB and present the structure of the DHp-CA catalytic core. Importantly, this structure shows a unique intramolecular cysteine disulfide bond in the ATP-binding domain that significantly affects autophosphorylation kinetics. In vitro data show that the redox state of the disulfide bond affects S. aureus biofilm formation and toxic shock syndrome toxin-1 production. Moreover, with the use of the rabbit infective endocarditis model, we demonstrate that the disulfide bond is a critical regulatory element of SrrB function during S. aureus infection. Our data support a model whereby the disulfide bond and PAS domain of SrrB sense and respond to the cellular redox environment to regulate S. aureus survival and pathogenesis.
Published: 2020

45. A Broad and Potent H1-Specific Human Monoclonal Antibody Produced in Plants Prevents Influenza Virus Infection and Transmission in Guinea Pigs

Author: New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), University of Rochester, Piepenbrink, Michael [0000-0001-7517-6412], Nogales, Aitor [0000-0002-2424-7900], Shuen, Michael [0000-0002-5223-412X], Meyers, Ashley J. [0000-0001-6427-472X], Martínez-Sobrido, Luis [0000-0001-7084-0804], Kobie, James J. [0000-0001-8069-0272], Park, Jun-Gyu, Ye, Chengjin, Piepenbrink, Michael, Nogales, Aitor, Wang, Haifeng, Shuen, Michael, Meyers, Ashley J., Martínez-Sobrido, Luis, Kobie, James J., New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), University of Rochester, Piepenbrink, Michael [0000-0001-7517-6412], Nogales, Aitor [0000-0002-2424-7900], Shuen, Michael [0000-0002-5223-412X], Meyers, Ashley J. [0000-0001-6427-472X], Martínez-Sobrido, Luis [0000-0001-7084-0804], Kobie, James J. [0000-0001-8069-0272], Park, Jun-Gyu, Ye, Chengjin, Piepenbrink, Michael, Nogales, Aitor, Wang, Haifeng, Shuen, Michael, Meyers, Ashley J., Martínez-Sobrido, Luis, and Kobie, James J.
Abstract: Although seasonal influenza vaccines block most predominant influenza types and subtypes, humans still remain vulnerable to waves of seasonal and new potential pandemic influenza viruses for which no immunity may exist because of viral antigenic drift and/or shift. Previously, we described a human monoclonal antibody (hMAb), KPF1, which was produced in human embryonic kidney 293T cells (KPF1-HEK) with broad and potent neutralizing activity against H1N1 influenza A viruses (IAV) in vitro, and prophylactic and therapeutic activities in vivo. In this study, we produced hMAb KPF1 in tobacco plants (KPF1-Antx) and demonstrated how the plant-produced KPF1-Antx hMAb possesses similar biological activity compared with the mammalian-produced KPF1-HEK hMAb. KPF1-Antx hMAb showed broad binding to recombinant HA proteins and H1N1 IAV, including A/California/04/2009 (pH1N1) in vitro, which was comparable to that observed with KPF1-HEK hMAb. Importantly, prophylactic administration of KPF1-Antx hMAb to guinea pigs prevented pH1N1 infection and transmission in both prophylactic and therapeutic experiments, substantiating its clinical potential to prevent and treat H1N1 infections. Collectively, this study demonstrated, for the first time, a plant-produced influenza hMAb with in vitro and in vivo activity against influenza virus. Because of the many advantages of plant-produced hMAbs, such as rapid batch production, low cost, and the absence of mammalian cell products, they represent an alternative strategy for the production of immunotherapeutics for the treatment of influenza viral infections, including emerging seasonal and/or pandemic strains.
Published: 2020

46. Safety and immunogenicity of a multivalent HIV vaccine comprising envelope protein with either DNA or NYVAC vectors (HVTN 096): a phase 1b, double-blind, placebo-controlled trial

Author: National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Bill & Melinda Gates Foundation, Pantaleo, Giuseppe, Janes, Holly, Karuna, Shelly, Grant, Shannon, Ouedraogo, G. Laissa, Allen, Mary, Tomaras, Georgia D., Frahm, Nicole, Montefiori, David C., Ferrari, Guido, Ding, Song, Lee, Carter, Robb, Merlin L., Esteban, Mariano, Wagner, Ralf, Bart, Pierre-Alexandre, Rettby, Nils, McElrath, J., Gilbert, Peter B., Kublin, James G., Corey, Lawrence, National Institutes of Health (US), National Institute of Allergy and Infectious Diseases (US), Bill & Melinda Gates Foundation, Pantaleo, Giuseppe, Janes, Holly, Karuna, Shelly, Grant, Shannon, Ouedraogo, G. Laissa, Allen, Mary, Tomaras, Georgia D., Frahm, Nicole, Montefiori, David C., Ferrari, Guido, Ding, Song, Lee, Carter, Robb, Merlin L., Esteban, Mariano, Wagner, Ralf, Bart, Pierre-Alexandre, Rettby, Nils, McElrath, J., Gilbert, Peter B., Kublin, James G., and Corey, Lawrence
Abstract: [Background]: Up to now, immunisation regimens that have been assessed for development of HIV vaccines have included purified envelope (Env) protein among the boosting components of the regimen. We postulated that co-administration of Env protein with either a DNA or NYVAC vector during priming would result in early generation of antibody responses to the Env V1/V2 region, which are important markers for effective protection against infection. We aimed to assess the safety and immunogenicity of a multivalent HIV vaccine including either DNA or NYVAC vectors alone or in combination with Env glycoprotein (gp120) followed by a co-delivered NYVAC and Env protein boost., [Methods]: We did a single-centre, double-blind, placebo-controlled phase 1b trial at the Centre Hospitalier Universitaire Vaudois (Lausanne, Switzerland). We included healthy volunteers aged 18–50 years who were at low risk of HIV infection. We randomly allocated participants using computer-generated random numbers to one of four vaccination schedules or placebo (4:1), and within these schedules participants were allocated either active treatment (T1, T2, T3, and T4) or placebo (C1, C2, C3, and C4). T1 consisted of two doses of NYVAC vector followed by two doses of NYVAC vector and gp120 Env protein; T2 comprised four doses of NYVAC vector and gp120 Env protein; T3 was two doses of DNA vector followed by two doses of NYVAC vector and gp120 Env protein; and T4 was two doses of DNA vector and gp120 Env protein followed by two doses of NYVAC vector and gp120 Env protein. Placebo injections were matched to the corresponding active treatment group. Doses were administered by injection at months 0, 1, 3, and 6. Primary outcomes were safety and immunogenicity of the vaccine schedules. Immune response measures included cross-clade and epitope-specific binding antibodies, neutralising antibodies, and antibody-dependent cell-mediated cytotoxicity measured 2 weeks after the month 1, 3, and 6 vaccinations. This trial is registered with ClinicalTrials.gov, NCT01799954., [Findings]: Between Aug 23, 2012, and April 18, 2013, 148 healthy adult volunteers were screened for the trial, of whom 96 participants were enrolled. 20 individuals were allocated to each active treatment group (groups T1–4; n=80) and four were assigned to each placebo group (groups C1–4; n=16). Vaccines containing the NYVAC vector (groups T1 and T2) were associated with more frequent severe reactogenicity and more adverse events than were vaccines containing the DNA vector (groups T3 and T4). The most frequent adverse events judged related to study product were lymphadenopathy (n=9) and hypoaesthesia (n=2). Two participants, one in the placebo group and one in the DNA-primed T3 group, had serious adverse events that were judged unrelated to study product. One participant in the T3 group died from cranial trauma after a motor vehicle accident. Across the active treatment groups, IgG responses 2 weeks after the 6-month dose of vaccine were 74–95%. Early administration of gp120 Env protein (groups T2 and T4) was associated with a substantially earlier and higher area under the curve for gp120 Env binding, production of anti-V1/V2 and neutralising antibodies, and better antibody-response coverage over a period of 18 months, compared with vaccination regimens that delayed administration of gp120 Env protein until the 3-month vaccination (groups T1 and T3)., [Interpretation]: Co-administration of gp120 Env protein components with DNA or NYVAC vectors during priming led to early and potent induction of Env V1/V2 IgG binding antibody responses. This immunisation approach should be considered for induction of preventive antibodies in future HIV vaccine efficacy trials.
Published: 2019

47. Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost

Author: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases (US), Asbach, Benedikt, Kibler, K., Köstler, Josef, Perdiguero, Beatriz, Yates, Nicole L., Stanfield-Oakley, Sherry, Tomaras, Georgia D., Kao, Shing-Fen, Foulds, Kathryn E., Roederer, Mario, Seaman, Michael S., Montefiori, David C., Parks, Robert, Ferrari, Guido, Forthal, Donald N., Phogat, Sanjay, Tartaglia, James, Barnett, Susan W., Self, Steven G., Gottardo, Raphael, Cristillo, Anthony D., Weiss, Deborah E., Galmin, Lindsey, Ding, Song, Heeney, Jonathan L., Esteban, Mariano, Jacobs, Bertram L., Pantaleo, Giuseppe, Wagner, Ralf, Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases (US), Asbach, Benedikt, Kibler, K., Köstler, Josef, Perdiguero, Beatriz, Yates, Nicole L., Stanfield-Oakley, Sherry, Tomaras, Georgia D., Kao, Shing-Fen, Foulds, Kathryn E., Roederer, Mario, Seaman, Michael S., Montefiori, David C., Parks, Robert, Ferrari, Guido, Forthal, Donald N., Phogat, Sanjay, Tartaglia, James, Barnett, Susan W., Self, Steven G., Gottardo, Raphael, Cristillo, Anthony D., Weiss, Deborah E., Galmin, Lindsey, Ding, Song, Heeney, Jonathan L., Esteban, Mariano, Jacobs, Bertram L., Pantaleo, Giuseppe, and Wagner, Ralf
Abstract: The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in nonhuman primates. In order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. Three groups of rhesus macaques were each primed with the same DNA vaccine encoding Gag, Pol, Nef, and gp140. The groups were then boosted with either the vaccinia virus strain NYVAC or a variant with improved replication competence in human cells, termed NYVAC-KC. The latter was administered either by scarification or intramuscularly. Finally, macaques were boosted with adjuvanted gp120 protein to enhance humoral responses. The regimen elicited very potent CD4+ and CD8+ T cell responses in a well-balanced manner, peaking 2 weeks after the boost. T cells were broadly reactive and polyfunctional. All animals exhibited antigen-specific humoral responses already after the poxvirus boost, which further increased following protein administration. Polyclonal reactivity of IgG antibodies was highest against HIV-1 clade C Env proteins, with considerable cross-reactivity to other clades. Substantial effector functional activities (antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated virus inhibition) were observed in serum obtained after the last protein boost. Notably, major differences between the groups were absent, indicating that the potent priming induced by the DNA vaccine initially framed the immune responses in such a way that the subsequent boosts with NYVAC and protein led only to an increase in the response magnitudes without skewing the quality. This study highlights the importance of selecting the best combination of vector systems in heterologous prime-boost vaccination regimens.
Published: 2019

48. Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC

Author: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases (US), Kibler, K., Asbach, Benedikt, Perdiguero, Beatriz, Yates, Nicole L., Parks, Robert, Stanfield-Oakley, Sherry, Ferrari, Guido, Montefiori, David C., Tomaras, Georgia D., Roederer, Mario, Foulds, Kathryn E., Forthal, Donald N., Seaman, Michael S., Self, Steve, Gottardo, Raphael, Phogat, Sanjay, Tartaglia, James, Barnett, Susan W., Cristillo, Anthony D., Weiss, Deborah E., Galmin, Lindsey, Ding, Song, Heeney, Jonathan L., Esteban, Mariano, Wagner, Ralf, Pantaleo, Giuseppe, Jacobs, Bertram L., Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases (US), Kibler, K., Asbach, Benedikt, Perdiguero, Beatriz, Yates, Nicole L., Parks, Robert, Stanfield-Oakley, Sherry, Ferrari, Guido, Montefiori, David C., Tomaras, Georgia D., Roederer, Mario, Foulds, Kathryn E., Forthal, Donald N., Seaman, Michael S., Self, Steve, Gottardo, Raphael, Phogat, Sanjay, Tartaglia, James, Barnett, Susan W., Cristillo, Anthony D., Weiss, Deborah E., Galmin, Lindsey, Ding, Song, Heeney, Jonathan L., Esteban, Mariano, Wagner, Ralf, Pantaleo, Giuseppe, and Jacobs, Bertram L.
Abstract: As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain NYVAC. NYVAC is a vector that has been used in many previous clinical studies but is replication deficient. Here, we report a side-by-side comparison of replication-restricted NYVAC and replication-competent NYVAC-KC in a nonhuman primate study, which utilized a prime-boost regimen similar to that of RV144. NYVAC-C and NYVAC-C-KC express the HIV-1 antigens gp140, and Gag/Gag-Pol-Nef-derived virus-like particles (VLPs) from clade C and were used as the prime, with recombinant virus plus envelope protein used as the boost. In nearly every T and B cell immune assay against HIV-1, including neutralization and antibody binding, NYVAC-C-KC induced a greater immune response than NYVAC-C, indicating that replication competence in a poxvirus may improve upon the modestly successful regimen used in the RV144 clinical trial.IMPORTANCE Though the RV144 phase III clinical trial showed promise that an effective vaccine against HIV-1 is possible, a successful vaccine will require improvement over the vaccine candidate (ALVAC) used in the RV144 study. With that goal in mind, we have tested in nonhuman primates an attenuated but replication-competent vector, NYVAC-KC, in direct comparison to its parental vector, NYVAC, which is replication restricted in human cells, similar to the ALVAC vector used in RV144. We have utilized a prime-boost regimen for administration of the vaccine candidate that is similar to the one used in the RV144 study. The results of this study indicate that a replication-competent poxvirus vector may improve upon the effectiveness of the RV144 clinical trial vaccine candidate.
Published: 2019

49. Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 3.0

Author: National Institutes of Health (US), Iranian National Science Foundation, Canadian Institutes of Health Research, Ministry of Health and Welfare (South Korea), Ministère de l’Enseignement supérieur et de la Recherche (France), National Eye Institute (US), National Human Genome Research Institute (US), National Heart, Lung, and Blood Institute (US), National Institute of Allergy and Infectious Diseases (US), National Institute of Diabetes and Digestive and Kidney Diseases (US), National Institute of General Medical Sciences (US), National Institute of Mental Health (US), Deutsch, Eric W., Lane, Lydie, Overall, Christopher M., Bandeira, Nuno, Baker, Mark S., Pineau, Charles, Moritz, Robert L., Corrales, Fernando J., Orchard, Sandra, Van Eyk, Jennifer E., Paik, Young-Ki, Weintraub, Susan T., Vandenbrouck, Yves, Omenn, Gilbert S., National Institutes of Health (US), Iranian National Science Foundation, Canadian Institutes of Health Research, Ministry of Health and Welfare (South Korea), Ministère de l’Enseignement supérieur et de la Recherche (France), National Eye Institute (US), National Human Genome Research Institute (US), National Heart, Lung, and Blood Institute (US), National Institute of Allergy and Infectious Diseases (US), National Institute of Diabetes and Digestive and Kidney Diseases (US), National Institute of General Medical Sciences (US), National Institute of Mental Health (US), Deutsch, Eric W., Lane, Lydie, Overall, Christopher M., Bandeira, Nuno, Baker, Mark S., Pineau, Charles, Moritz, Robert L., Corrales, Fernando J., Orchard, Sandra, Van Eyk, Jennifer E., Paik, Young-Ki, Weintraub, Susan T., Vandenbrouck, Yves, and Omenn, Gilbert S.
Abstract: The Human Proteome Organization’s (HUPO) Human Proteome Project (HPP) developed Mass Spectrometry (MS) Data Interpretation Guidelines that have been applied since 2016. These guidelines have helped ensure that the emerging draft of the complete human proteome is highly accurate and with low numbers of false-positive protein identifications. Here, we describe an update to these guidelines based on consensus-reaching discussions with the wider HPP community over the past year. The revised 3.0 guidelines address several major and minor identified gaps. We have added guidelines for emerging data independent acquisition (DIA) MS workflows and for use of the new Universal Spectrum Identifier (USI) system being developed by the HUPO Proteomics Standards Initiative (PSI). In addition, we discuss updates to the standard HPP pipeline for collecting MS evidence for all proteins in the HPP, including refinements to minimum evidence. We present a new plan for incorporating MassIVE-KB into the HPP pipeline for the next (HPP 2020) cycle in order to obtain more comprehensive coverage of public MS data sets. The main checklist has been reorganized under headings and subitems, and related guidelines have been grouped. In sum, Version 2.1 of the HPP MS Data Interpretation Guidelines has served well, and this timely update to version 3.0 will aid the HPP as it approaches its goal of collecting and curating MS evidence of translation and expression for all predicted ∼20 000 human proteins encoded by the human genome.
Published: 2019

50. Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo

Author: Centers of Excellence for Influenza Research and Surveillance (US), National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Defense (US), Nogales, Aitor, Aydillo, Teresa, Ávila-Pérez, Ginés, Escalera, Alba, Chiem, Kevin, Cadagan, Richard, DeDiego, Marta L., Li, Feng, García-Sastre, Adolfo, Martínez-Sobrido, Luis, Centers of Excellence for Influenza Research and Surveillance (US), National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Defense (US), Nogales, Aitor, Aydillo, Teresa, Ávila-Pérez, Ginés, Escalera, Alba, Chiem, Kevin, Cadagan, Richard, DeDiego, Marta L., Li, Feng, García-Sastre, Adolfo, and Martínez-Sobrido, Luis
Abstract: Influenza viruses are important pathogens that affect multiple animal species, including humans. There are four types of influenza viruses: A, B, C, and D (IAV, IBV, ICV, and IDV, respectively). IAV and IBV are currently circulating in humans and are responsible of seasonal epidemics (IAV and IBV) and occasional pandemics (IAV). ICV is known to cause mild infections in humans and pigs, while the recently identified IDV primarily affect cattle and pigs. Influenza non-structural protein 1 (NS1) is a multifunctional protein encoded by the NS segment in all influenza types. The main function of NS1 is to counteract the host antiviral defense, including the production of interferon (IFN) and IFN-stimulated genes (ISGs), and therefore is considered an important viral pathogenic factor. Despite of homologous functions, the NS1 protein from the diverse influenza types share little amino acid sequence identity, suggesting possible differences in their mechanism(s) of action, interaction(s) with host factors, and contribution to viral replication and/or pathogenesis. In addition, although the NS1 protein of IAV, IBV and, to some extent ICV, have been previously studied, it is unclear if IDV NS1 has similar properties. Using an approach that allow us to express NS1 independently of the nuclear export protein from the viral NS segment, we have generated recombinant IAV expressing IAV, IBV, ICV, and IDV NS1 proteins. Although recombinant viruses expressing heterotypic (IBV, ICV, and IDV) NS1 proteins were able to replicate similarly in canine MDCK cells, their viral fitness was impaired in human A549 cells and they were highly attenuated in vivo. Our data suggest that despite the similarities to effectively counteract innate immune responses in vitro, the NS1 proteins of IBV, ICV, or IDV do not fully complement the functions of IAV NS1, resulting in deficient viral replication and pathogenesis in vivo.
Published: 2019

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