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1. Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection

Author

Santos-Peral, Antonio, Luppa, Fabian, Goresch, Sebastian, Nikolova, Elena, Zaucha, Magdalena, Lehmann, Lisa, Dahlstroem, Frank, Karimzadeh, Hadi, Thorn-Seshold, Julia, Winheim, Elena, Schuster, Ev-Marie, Dobler, Gerhard, Hoelscher, Michael, Kümmerer, Beate M., Endres, Stefan, Schober, Kilian, Krug, Anne B., Pritsch, Michael, Barba-Spaeth, Giovanna, and Rothenfusser, Simon

Published
2024
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2. Dissecting human population variation in single-cell responses to SARS-CoV-2

Author

Aquino, Yann, Bisiaux, Aurélie, Li, Zhi, O’Neill, Mary, Mendoza-Revilla, Javier, Merkling, Sarah Hélène, Kerner, Gaspard, Hasan, Milena, Libri, Valentina, Bondet, Vincent, Smith, Nikaïa, de Cevins, Camille, Ménager, Mickaël, Luca, Francesca, Pique-Regi, Roger, Barba-Spaeth, Giovanna, Pietropaoli, Stefano, Schwartz, Olivier, Leroux-Roels, Geert, Lee, Cheuk-Kwong, Leung, Kathy, Wu, Joseph T., Peiris, Malik, Bruzzone, Roberto, Abel, Laurent, Casanova, Jean-Laurent, Valkenburg, Sophie A., Duffy, Darragh, Patin, Etienne, Rotival, Maxime, and Quintana-Murci, Lluis

Published
2023
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3. SARS-CoV-2 Omicron BA.1 breakthrough infection drives late remodeling of the memory B cell repertoire in vaccinated individuals

Author

Sokal, Aurélien, Barba-Spaeth, Giovanna, Hunault, Lise, Fernández, Ignacio, Broketa, Matteo, Meola, Annalisa, Fourati, Slim, Azzaoui, Imane, Vandenberghe, Alexis, Lagouge-Roussey, Pauline, Broutin, Manon, Roeser, Anais, Bouvier-Alias, Magali, Crickx, Etienne, Languille, Laetitia, Fournier, Morgane, Michel, Marc, Godeau, Bertrand, Gallien, Sébastien, Melica, Giovanna, Nguyen, Yann, Canoui-Poitrine, Florence, Pirenne, France, Megret, Jérôme, Pawlotsky, Jean-Michel, Fillatreau, Simon, Reynaud, Claude-Agnès, Weill, Jean-Claude, Rey, Félix A., Bruhns, Pierre, Mahévas, Matthieu, and Chappert, Pascal

Published
2023
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4. Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine

Author

Wec, Anna Z., Haslwanter, Denise, Abdiche, Yasmina N., Shehata, Laila, Pedreño-Lopez, Nuria, Moyer, Crystal L., Bornholdt, Zachary A., Lilov, Asparouh, Nett, Juergen H., Jangra, Rohit K., Brown, Michael, Watkins, David I., Ahlm, Clas, Forsell, Mattias N., Rey, Félix A., Barba-Spaeth, Giovanna, Chandran, Kartik, and Walker, Laura M.

Published
2020

5. Defective viral genomes as therapeutic interfering particles against flavivirus infection in mammalian and mosquito hosts

Author

Rezelj, Veronica V., Carrau, Lucía, Merwaiss, Fernando, Levi, Laura I., Erazo, Diana, Tran, Quang Dinh, Henrion-Lacritick, Annabelle, Gausson, Valérie, Suzuki, Yasutsugu, Shengjuler, Djoshkun, Meyer, Bjoern, Vallet, Thomas, Weger-Lucarelli, James, Bernhauerová, Veronika, Titievsky, Avi, Sharov, Vadim, Pietropaoli, Stefano, Diaz-Salinas, Marco A., Legros, Vincent, Pardigon, Nathalie, Barba-Spaeth, Giovanna, Brodsky, Leonid, Saleh, Maria-Carla, and Vignuzzi, Marco

Published
2021
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6. Prior flavivirus immunity skews the yellow fever vaccine response to expand cross-reactive antibodies with increased risk of antibody dependent enhancement of Zika and dengue virus infection

Author

Santos-Peral, Antonio, primary, Luppa, Fabian, additional, Goresch, Sebastian, additional, Nikolova, Elena, additional, Zaucha, Magdalena, additional, Lehmann, Lisa, additional, Dahlstroem, Frank, additional, Karimzadeh, Hadi, additional, Kummerer, Beate M, additional, Thorn-Seshold, Julia, additional, Winheim, Elena, additional, Dobler, Gerhard, additional, Hoelscher, Michael, additional, Endres, Stefan, additional, Krug, Anne B, additional, Pritsch, Michael, additional, Barba-Spaeth, Giovanna, additional, and Rothenfusser, Simon, additional

Published
2023
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7. A specific molecular signature in SARS-CoV-2–infected kidney biopsies

Author

Isnard, Pierre, primary, Vergnaud, Paul, additional, Garbay, Serge, additional, Jamme, Matthieu, additional, Eloudzeri, Maeva, additional, Karras, Alexandre, additional, Anglicheau, Dany, additional, Galantine, Valérie, additional, Jalal Eddine, Arwa, additional, Gosset, Clément, additional, Pourcine, Franck, additional, Zarhrate, Mohammed, additional, Gibier, Jean-Baptiste, additional, Rensen, Elena, additional, Pietropaoli, Stefano, additional, Barba-Spaeth, Giovanna, additional, Duong-Van-Huyen, Jean-Paul, additional, Molina, Thierry J., additional, Mueller, Florian, additional, Zimmer, Christophe, additional, Pontoglio, Marco, additional, Terzi, Fabiola, additional, and Rabant, Marion, additional

Published
2023
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8. Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals

Author

Sokal, Aurélien, primary, Barba-Spaeth, Giovanna, additional, Hunault, Lise, additional, Fernández, Ignacio, additional, Broketa, Matteo, additional, Meola, Annalisa, additional, Fourati, Slim, additional, Azzaoui, Imane, additional, Vandenberghe, Alexis, additional, Lagouge-Roussey, Pauline, additional, Broutin, Manon, additional, Roeser, Anais, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Fournier, Morgane, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Canoui-Poitrine, Florence, additional, Noizat-Pirenne, France, additional, Megret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Reynaud, Claude-Agnès, additional, Weill, Jean-Claude, additional, Rey, Félix A., additional, Bruhns, Pierre, additional, Mahévas, Matthieu, additional, and Chappert, Pascal, additional

Published
2023
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9. Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals

Author

Sokal, Aurélien, Barba-Spaeth, Giovanna, Hunault, Lise, Fernández, Ignacio, Broketa, Matteo, Meola, Annalisa, Fourati, Slim, Azzaoui, Imane, Vandenberghe, Alexis, Lagouge-Roussey, Pauline, Broutin, Manon, Roeser, Anais, Bouvier-Alias, Magali, Crickx, Etienne, Languille, Laetitia, Fournier, Morgane, Michel, Marc, Godeau, Bertrand, Gallien, Sébastien, Melica, Giovanna, Nguyen, Yann, Canoui-Poitrine, Florence, Noizat-Pirenne, France, Megret, Jérôme, Pawlotsky, Jean-Michel, Fillatreau, Simon, Reynaud, Claude-Agnès, Weill, Jean-Claude, Rey, Félix, Bruhns, Pierre, Mahévas, Matthieu, Chappert, Pascal, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Physiologie, physiopathologie et thérapeutique (ED 394), Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etablissement Français du Sang [Créteil], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and This work was funded by the CAPNET (Comité ad-hoc de pilotage national des essaisthérapeutiques et autres recherches, French government) and by the Fondation PrincesseGrace. Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Cli-nique et du Développement) was the promotor and sponsor of MEMO-COV-2. Work in theUnit of Structural Virology was funded by Institut Pasteur, Urgence COVID-19 FundraisingCampaign of Institut Pasteur. PB acknowledges funding from the Institut Pasteur and InsitutNational de la Santé et de la Recherche Médicale (INSERM). AS was supported by a Posted’accueil from INSERM.

Subjects
[SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

SummaryHow infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limitedde novoresponse against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies.

Published
2023

10. Environmental and genetic drivers of population differences in SARS-CoV-2 immune responses

Author

Aquino, Yann, primary, Bisiaux, Aurélie, additional, Li, Zhi, additional, O’Neill, Mary, additional, Mendoza-Revilla, Javier, additional, Merkling, Sarah Hélène, additional, Kerner, Gaspard, additional, Hasan, Milena, additional, Libri, Valentina, additional, Bondet, Vincent, additional, Smith, Nikaïa, additional, de Cevins, Camille, additional, Ménager, Mickaël, additional, Luca, Francesca, additional, Pique-Regi, Roger, additional, Barba-Spaeth, Giovanna, additional, Pietropaoli, Stefano, additional, Schwartz, Olivier, additional, Leroux-Roels, Geert, additional, Lee, Cheuk-Kwong, additional, Leung, Kathy, additional, Wu, Joseph T.K., additional, Peiris, Malik, additional, Bruzzone, Roberto, additional, Abel, Laurent, additional, Casanova, Jean-Laurent, additional, Valkenburg, Sophie A., additional, Duffy, Darragh, additional, Patin, Etienne, additional, Rotival, Maxime, additional, and Quintana-Murci, Lluis, additional

Published
2022
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11. Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination

Author

Sokal, Aurélien, primary, Bastard, Paul, additional, Chappert, Pascal, additional, Barba-Spaeth, Giovanna, additional, Fourati, Slim, additional, Vanderberghe, Alexis, additional, Lagouge-Roussey, Pauline, additional, Meyts, Isabelle, additional, Gervais, Adrian, additional, Bouvier-Alias, Magali, additional, Azzaoui, Imane, additional, Fernández, Ignacio, additional, de la Selle, Andréa, additional, Zhang, Qian, additional, Bizien, Lucy, additional, Pellier, Isabelle, additional, Linglart, Agnès, additional, Rothenbuhler, Anya, additional, Marcoux, Estelle, additional, Anxionnat, Raphael, additional, Cheikh, Nathalie, additional, Léger, Juliane, additional, Amador-Borrero, Blanca, additional, Fouyssac, Fanny, additional, Menut, Vanessa, additional, Goffard, Jean-Christophe, additional, Storey, Caroline, additional, Demily, Caroline, additional, Mallebranche, Coralie, additional, Troya, Jesus, additional, Pujol, Aurora, additional, Zins, Marie, additional, Tiberghien, Pierre, additional, Gray, Paul E., additional, McNaughton, Peter, additional, Sullivan, Anna, additional, Peake, Jane, additional, Levy, Romain, additional, Languille, Laetitia, additional, Rodiguez-Gallego, Carlos, additional, Boisson, Bertrand, additional, Gallien, Sébastien, additional, Neven, Bénédicte, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Abel, Laurent, additional, Rey, Felix A., additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, Tangye, Stuart G., additional, Casanova, Jean-Laurent, additional, and Mahévas, Matthieu, additional

Published
2022
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12. Molecular mechanisms regulating the pH-dependent pr/E interaction in yellow fever virus

Author

Crampon, E., Covernton, E., Vaney, M.C., Dellarole, M., Sharma, A., Haouz, A., England, P., Lepault, J., Duquerroy, S., Rey, F.A., Barba-Spaeth, Giovanna, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cristallographie (Plateforme) - Crystallography (Platform), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), This work was supported by the French ANR (Agence Nationale de la Recherche), grants ANR-17-CE15-0031-01 FLAVIMMUNITY to GBS., We thank the staff at beamlines PX1 and PX2 at Soleil synchrotron (St. Aubin, France) and at PX beamlines at the ESRF (Grenoble, France), Franz X. Heinz and Karin Stiasny from Center for Virology, Medical University of Vienna, Austria for the gift of DENV pr protein and the plasmid for the production of ZIKV PF13 sE protein, Pablo Guardado-Calvo and Ignacio Fernandez from the Rey lab for helping with the MALS experiments and Alexander Rouvinski for help with the setting of the fusion experiments., and ANR-17-CE15-0031,FLAVIMMUNITY,Comprendre les mécanismes de l'efficacité du vaccin de la fièvre jaune 17D: Une approche immuno-structurelle vers la conception d'un vaccin Pan-flavivirus(2017)

Subjects
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV]Life Sciences [q-bio]
Abstract

Flavivirus particles bud in the ER of infected cells as immature virions composed of 180 heterodimers of glycoproteins prM and E, associated as 60 (prM/E)3trimeric spikes. Exposure to the mildly acidic pH of the TGN results in dissociation of the trimeric spikes followed by reassociation of the prM/E protomers into 90 dimers organized in a characteristic herringbone pattern. The furin site in prM is exposed in the dimers for maturation of prM into M and pr. For flaviviruses such as the tick-borne encephalitis virus (TBEV) as well as for dengue virus, it was shown that at neutral pH pr loses affinity for E, such that it dissociates from the mature particle as soon as it reaches the external milieu, which is at neutral pH. Using a soluble recombinant form of E (sE) and pr from yellow fever virus (YFV), we show here that the affinity of pr for recombinant E protein remains high even at neutral pH. The X-ray structure of YFV pr/sE shows more extensive inter-chain hydrogen bonding than does the dengue or TBEV, and also that it retains the charge complementarity between the interacting surfaces of the two proteins even at neutral pH. We further show that pr blocks sE flotation with liposomes when exposed at low pH at a 1:1 stoichiometry, yet in the context of the virus particle, an excess of 10:1 pr:E ratio is required to block virus/liposome fusion. In aggregate, our results show that the paradigm obtained from earlier studies of other flaviviruses does not apply to yellow fever virus, the flavivirus type species. A mechanism that does not rely solely in a change in the environmental pH is thus required for the release of pr from the mature particles upon release from infected cells. These results open up new avenues to understand the activation mechanism that yields mature, infectious YFV particles.

Published
2022

14. Structural basis of potent Zika-dengue virus antibody cross-neutralization

Author

Barba-Spaeth, Giovanna, Dejnirattisai, Wanwisa, Rouvinski, Alexander, Vaney, Marie-Christine, Medits, Iris, Sharma, Arvind, Simon-Loriere, Etienne, Sakuntabhai, Anavaj, Cao-Lormeau, Van-Mai, Haouz, Ahmed, England, Patrick, Stiasny, Karin, Mongkolsapaya, Juthathip, Heinz, Franz X., Screaton, Gavin R., and Rey, Felix A.

Subjects
Guillain-Barre syndrome -- Research -- Health aspects, Viral antibodies -- Research -- Health aspects, Antibodies -- Research -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Zika virus is a member of the Flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in Brazil and to Guillain-Barre syndrome in adults in French Polynesia. Zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize Zika virus. The crystal structure of two of these antibodies in complex with the envelope protein of Zika virus reveals the details of a conserved epitope, which is also the site of interaction of the envelope protein dimer with the precursor membrane (prM) protein during virus maturation. Comparison of the Zika and dengue virus immunocomplexes provides a lead for rational, epitope-focused design of a universal vaccine capable of eliciting potent cross-neutralizing antibodies to protect simultaneously against both Zika and dengue virus infections., Zika virus (ZIKV) is an arthropod-borne enveloped virus belonging to the Flavivirus genus in the family Flaviviridae, which also includes the human pathogenic yellow fever, dengue, West Nile and tick-borne [...]

Published
2016
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16. Analysis of mRNA vaccination-elicited RBD-specific memory B cells reveals strong but incomplete immune escape of the SARS-CoV-2 Omicron variant

Author

Sokal, Aurélien, primary, Broketa, Matteo, additional, Barba-Spaeth, Giovanna, additional, Meola, Annalisa, additional, Fernández, Ignacio, additional, Fourati, Slim, additional, Azzaoui, Imane, additional, de La Selle, Andrea, additional, Vandenberghe, Alexis, additional, Roeser, Anais, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Zarrouk, Virginie, additional, Canoui-Poitrine, Florence, additional, Noizat-Pirenne, France, additional, Megret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Simon-Lorière, Etienne, additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, Rey, Félix A., additional, Bruhns, Pierre, additional, Chappert, Pascal, additional, and Mahévas, Matthieu, additional

Published
2022
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17. Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Author

Rouvinski, Alexander, Guardado-Calvo, Pablo, Barba-Spaeth, Giovanna, Duquerroy, Stephane, Vaney, Marie- Christine, Kikuti, Carlos M., Sanchez, M. Erika Navarro, Dejnirattisai, Wanwisa, Wongwiwat, Wiyada, Haouz, Ahmed, Girard- Blanc, Christine, Petres, Stephane, Shepard, William E., Despres, Philippe, Arenzana-Seisdedos, Fernando, Dussart, Philippe, Mongkolsapaya, Juthathip, Screaton, Gavin R., and Rey, Felix A.

Subjects
Viral antibodies -- Health aspects, Antigenic determinants -- Health aspects, Dengue viruses -- Health aspects, Antibodies -- Health aspects, Host-virus relationships -- Identification and classification, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Dengue disease is caused by four different flavivirus (1) serotypes, which infect 390 million people yearly with 25% symptomatic cases (2) and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3,4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies (5,6). We recently isolated human antibodies potently neutralizing all four dengue virus serotypes (7). Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop (8) and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell (9), explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus., Exposed at the surface of infectious mature dengue virus (DENV) particles, protein E is the sole target of neutralizing antibodies. It displays an icosahedral arrangement in which 90 E dimers [...]

Published
2015

18. FluoRNT: A robust, efficient assay for the detection of neutralising antibodies against yellow fever virus 17D

Author

Scheck, Magdalena K., primary, Lehmann, Lisa, additional, Zaucha, Magdalena, additional, Schwarzlmueller, Paul, additional, Huber, Kristina, additional, Pritsch, Michael, additional, Barba-Spaeth, Giovanna, additional, Thorn-Seshold, Oliver, additional, Krug, Anne B., additional, Endres, Stefan, additional, Rothenfusser, Simon, additional, and Thorn-Seshold, Julia, additional

Published
2022
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19. Sensitive visualization of SARS-CoV-2 RNA with CoronaFISH

Author

Rensen, Elena, primary, Pietropaoli, Stefano, additional, Mueller, Florian, additional, Weber, Christian, additional, Souquere, Sylvie, additional, Sommer, Sina, additional, Isnard, Pierre, additional, Rabant, Marion, additional, Gibier, Jean-Baptiste, additional, Terzi, Fabiola, additional, Simon-Loriere, Etienne, additional, Rameix-Welti, Marie-Anne, additional, Pierron, Gérard, additional, Barba-Spaeth, Giovanna, additional, and Zimmer, Christophe, additional

Published
2022
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20. Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells.

Author

Sokal, Aurelien, primary, Broketa, Matteo, additional, Meola, Annalisa, additional, Barba-Spaeth, Giovanna, additional, Fernandez, Ignacio, additional, Fourati, Slim, additional, Azzaoui, Imane, additional, de La Selle, Andrea, additional, Vandenberghe, Alexis, additional, Roeser, Anais, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sebastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Zarrouk, Virginie, additional, Canoui-Poitrine, Florence, additional, Noizat-Pirenne, France, additional, Megret, Jerome, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Simon-Loriere, Etienne, additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnes, additional, Rey, Felix A., additional, Bruhns, Pierre, additional, Chappert, Pascal, additional, and Mahevas, Matthieu, additional

Published
2021
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21. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants

Author

Sokal, Aurélien, primary, Barba-Spaeth, Giovanna, additional, Fernández, Ignacio, additional, Broketa, Matteo, additional, Azzaoui, Imane, additional, de La Selle, Andréa, additional, Vandenberghe, Alexis, additional, Fourati, Slim, additional, Roeser, Anais, additional, Meola, Annalisa, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Zarrouk, Virginie, additional, Canoui-Poitrine, Florence, additional, Pirenne, France, additional, Mégret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Bruhns, Pierre, additional, Rey, Felix A., additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, Chappert, Pascal, additional, and Mahévas, Matthieu, additional

Published
2021
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23. La diversité du répertoire des cellules B mémoires fait face aux variants du SRAS-CoV2 après la vaccination par ARNm chez les individus naïfs et guéris

Author

Chappert, Pascal, primary, Sokal, Aurélien, additional, Barba-Spaeth, Giovanna, additional, Fernandez, Ignacio, additional, Broketta, Matteo, additional, Azzaoui, Imane, additional, De La Selle, Andrea, additional, Vandenberghe, Alexis, additional, Fourati, Slim, additional, Meola, Annalisa, additional, Bouvier-Alias, Magali, additional, Cricks, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Canoui-Poitrine, Florence, additional, Pirenne, France, additional, Megret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Bruhns, Pierre, additional, Rey, Felix, additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, and Mahévas, Matthieu, additional

Published
2021
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24. Functional and evolutionary insight from the crystal structure of rubella virus protein E1

Author

DuBois, Rebecca M., Vaney, Marie-Christine, Tortorici, M. Alejandra, Al Kurdi, Rana, Barba-Spaeth, Giovanna, Krey, Thomas, and Rey, Felix A.

Subjects
Crystals -- Structure, Rubella -- Natural history -- Physiological aspects -- Health aspects -- Research, Viral proteins -- Structure -- Research -- Health aspects -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Little is known about the three-dimensional organization of rubella virus, which causes a relatively mild measles-like disease in children but leads to serious congenital health problems when contracted in utero [...]

Published
2013
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25. Memory B cells control SARS-CoV-2 variants upon mRNA vaccination of naive and COVID-19 recovered individuals

Author

Sokal, Aurélien, primary, Barba-Spaeth, Giovanna, additional, Fernández, Ignacio, additional, Broketa, Matteo, additional, Azzaoui, Imane, additional, La Selle, Andrea de, additional, Vandenberghe, Alexis, additional, Fourati, Slim, additional, Roeser, Anais, additional, Meola, Annalisa, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Languille, Laetitia, additional, Michel, Marc, additional, Godeau, Bertrand, additional, Gallien, Sébastien, additional, Melica, Giovanna, additional, Nguyen, Yann, additional, Zarrouk, Virginie, additional, Canoui-Poitrine, Florence, additional, Noizat-Pirenne, France, additional, Megret, Jérôme, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Bruhns, Pierre, additional, Rey, Felix A., additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, Chappert, Pascal, additional, and Mahévas, Matthieu, additional

Published
2021
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26. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Author

Sokal, Aurélien, primary, Chappert, Pascal, additional, Barba-Spaeth, Giovanna, additional, Roeser, Anais, additional, Fourati, Slim, additional, Azzaoui, Imane, additional, Vandenberghe, Alexis, additional, Fernandez, Ignacio, additional, Meola, Annalisa, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Beldi-Ferchiou, Asma, additional, Hue, Sophie, additional, Languille, Laetitia, additional, Michel, Marc, additional, Baloul, Samia, additional, Noizat-Pirenne, France, additional, Luka, Marine, additional, Mégret, Jérôme, additional, Ménager, Mickaël, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Rey, Felix A., additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, and Mahévas, Matthieu, additional

Published
2021
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27. Sensitive visualization of SARS-CoV-2 RNA with CoronaFISH

Author

Rensen, Elena, primary, Pietropaoli, Stefano, additional, Mueller, Florian, additional, Weber, Christian, additional, Souquere, Sylvie, additional, Isnard, Pierre, additional, Rabant, Marion, additional, Gibier, Jean-Baptiste, additional, Simon-Loriere, Etienne, additional, Rameix-Welti, Marie-Anne, additional, Pierron, Gérard, additional, Barba-Spaeth, Giovanna, additional, and Zimmer, Christophe, additional

Published
2021
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28. Erratum: Structural basis of potent Zikadengue virus antibody cross-neutralization

Author

Barba-Spaeth, Giovanna, Dejnirattisai, Wanwisa, Rouvinski, Alexander, Vaney, Marie-Christine, Medits, Iris, Sharma, Arvind, Simon-Lorire, Etienne, Sakuntabhai, Anavaj, Cao-Lormeau, Van-Mai, Haouz, Ahmed, England, Patrick, Stiasny, Karin, Mongkolsapaya, Juthathip, Heinz, Franz X., Screaton, Gavin R., and Rey, Flix A.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Giovanna Barba-Spaeth; Wanwisa Dejnirattisai; Alexander Rouvinski; Marie-Christine Vaney; Iris Medits; Arvind Sharma; Etienne Simon-Lorire; Anavaj Sakuntabhai; Van-Mai Cao-Lormeau; Ahmed Haouz; Patrick England; Karin Stiasny; Juthathip Mongkolsapaya; Franz X. Heinz; [...]

Published
2016
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29. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Author

Sokal, Aurélien, primary, Chappert, Pascal, additional, Roeser, Anais, additional, Barba-Spaeth, Giovanna, additional, Fourati, Slim, additional, Azzaoui, Imane, additional, Vandenberghe, Alexis, additional, Fernandez, Ignacio, additional, Bouvier-Alias, Magali, additional, Crickx, Etienne, additional, Ferchiou, Asma Beldi, additional, Hue, Sophie, additional, Languille, Laetitia, additional, Baloul, Samia, additional, Noizat-Pirenne, France, additional, Luka, Marine, additional, Megret, Jérôme, additional, Ménager, Mickaël, additional, Pawlotsky, Jean-Michel, additional, Fillatreau, Simon, additional, Rey, Felix A, additional, Weill, Jean-Claude, additional, Reynaud, Claude-Agnès, additional, and Mahévas, Matthieu, additional

Published
2020
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30. Dynamic changes in circulating T follicular helper cell composition predict neutralising antibody responses after yellow fever vaccination

Author

Huber, Johanna E, primary, Ahlfeld, Julia, additional, Scheck, Magdalena K, additional, Zaucha, Magdalena, additional, Witter, Klaus, additional, Lehmann, Lisa, additional, Karimzadeh, Hadi, additional, Pritsch, Michael, additional, Hoelscher, Michael, additional, Sonnenburg, Frank, additional, Dick, Andrea, additional, Barba‐Spaeth, Giovanna, additional, Krug, Anne B, additional, Rothenfußer, Simon, additional, and Baumjohann, Dirk, additional

Published
2020
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31. Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope

Author

Rouvinski, Alexander, Dejnirattisai, Wanwisa, Guardado-Calvo, Pablo, Vaney, Marie-Christine, Sharma, Arvind, Duquerroy, Stéphane, Supasa, Piyada, Wongwiwat, Wiyada, Haouz, Ahmed, Barba-Spaeth, Giovanna, Mongkolsapaya, Juthathip, Rey, Félix A., Screaton, Gavin R., Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Division of Immunology and Inflammation, Department of Medicine, Imperial College London-Hammersmith Hospital Campus, Protéopole, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], We acknowledge support from the European Commission FP7 Programme for the DENFREE project under Grant Agreement number 282 378FP7 (F.A.R., J.M. and G.R.S.), the ‘Integrative Biology of Emerging Infectious Diseases’ Labex (Laboratoire d’Excellence) grant number ANR-10-LABX-62-IBEID (French Government’s ‘Investissements d’Avenir’ program ) (F.A.R.) the National Institute for Health Research Biomedical Research Centre, Funding Scheme, UK (G.R.S.), and the NEUTRAVIR grant from Région Ile-de-France (DIM-Maladies Infectieuses) (F.A.R.). G.R.S. is a Wellcome Trust Senior Investigator., We thank Watchara Kasinrerk and Chunya Putthikhunt for anti-dengue anti-DomIII mAb 2C8, J. Freire and G. Bowler for help and discussion, the staff at the crystallogenesis and chemogenomic & biological screening facilities at Institut Pasteur, the staff at beamlines PX1 and PX2 at SOLEIL synchrotron (Saclay, France), the staff at beamlines ID23-1, ID23-2, ID29 and IB30B at the European Synchrotron Radiation Facility (Grenoble, France), Fabrice Agou at Institut Pasteur for the MALS system., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
STRUCTURAL BASIS, MONOCLONAL-ANTIBODY, [SDV]Life Sciences [q-bio], Science, Enzyme-Linked Immunosorbent Assay, Antibodies, Viral, Crystallography, X-Ray, CROSS-NEUTRALIZATION, Article, Dengue virus, NEUTRALIZING ANTIBODIES, Mice, Protein Domains, Viral Envelope Proteins, Aedes, Chlorocebus aethiops, INFECTION, MD Multidisciplinary, Animals, Humans, Disulfides, Vero Cells, ANTIBODY-DEPENDENT ENHANCEMENT, X-ray crystallography, Vaccines, Science & Technology, Immunodominant Epitopes, HIGHLY POTENT, MACROMOLECULAR CRYSTALLOGRAPHY, Antibodies, Monoclonal, SEROTYPE 3, Antibodies, Neutralizing, Multidisciplinary Sciences, HEK293 Cells, Viral infection, Liposomes, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Science & Technology - Other Topics, Drosophila, Protein Multimerization, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, ZIKA VIRUS, Epitope Mapping
Abstract

A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic ‘breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing. We here engineer E dimers locked by inter-subunit disulfide bonds, and show by X-ray crystallography and by binding to a panel of human antibodies that these engineered dimers do not expose the FLE, while retaining the EDE exposure. These locked dimers are strong immunogen candidates for a next-generation vaccine., The immunodominant epitope of dengue virus envelope protein (E) induces poorly neutralizing antibodies, which poses a problem for vaccine development. Here, the authors engineer covalently locked E dimers exposing an epitope that has been shown to induce potent and broadly neutralizing antibodies.

Published
2017

32. Inhibition of Polyamine Biosynthesis Is a Broad-Spectrum Strategy against RNA Viruses

Author

Mounce, Bryan C., primary, Cesaro, Teresa, additional, Moratorio, Gonzalo, additional, Hooikaas, Peter Jan, additional, Yakovleva, Anna, additional, Werneke, Scott W., additional, Smith, Everett Clinton, additional, Poirier, Enzo Z., additional, Simon-Loriere, Etienne, additional, Prot, Matthieu, additional, Tamietti, Carole, additional, Vitry, Sandrine, additional, Volle, Romain, additional, Khou, Cécile, additional, Frenkiel, Marie-Pascale, additional, Sakuntabhai, Anavaj, additional, Delpeyroux, Francis, additional, Pardigon, Nathalie, additional, Flamand, Marie, additional, Barba-Spaeth, Giovanna, additional, Lafon, Monique, additional, Denison, Mark R., additional, Albert, Matthew L., additional, and Vignuzzi, Marco, additional

Published
2016
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33. Erratum: Structural basis of potent Zika–dengue virus antibody cross-neutralization

Author

Barba-Spaeth, Giovanna, primary, Dejnirattisai, Wanwisa, additional, Rouvinski, Alexander, additional, Vaney, Marie-Christine, additional, Medits, Iris, additional, Sharma, Arvind, additional, Simon-Lorière, Etienne, additional, Sakuntabhai, Anavaj, additional, Cao-Lormeau, Van-Mai, additional, Haouz, Ahmed, additional, England, Patrick, additional, Stiasny, Karin, additional, Mongkolsapaya, Juthathip, additional, Heinz, Franz X., additional, Screaton, Gavin R., additional, and Rey, Félix A., additional

Published
2016
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34. Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination

Author

Sokal, Aurélien, Bastard, Paul, Chappert, Pascal, Barba-Spaeth, Giovanna, Fourati, Slim, Vanderberghe, Alexis, Lagouge-Roussey, Pauline, Meyts, Isabelle, Gervais, Adrian, Bouvier-Alias, Magali, Azzaoui, Imane, Fernández, Ignacio, de la Selle, Andréa, Zhang, Qian, Bizien, Lucy, Pellier, Isabelle, Linglart, Agnès, Rothenbuhler, Anya, Marcoux, Estelle, Anxionnat, Raphael, Cheikh, Nathalie, Léger, Juliane, Amador-Borrero, Blanca, Fouyssac, Fanny, Menut, Vanessa, Goffard, Jean-Christophe, Storey, Caroline, Demily, Caroline, Mallebranche, Coralie, Troya, Jesus, Pujol, Aurora, Zins, Marie, Tiberghien, Pierre, Gray, Paul E., McNaughton, Peter, Sullivan, Anna, Peake, Jane, Levy, Romain, Languille, Laetitia, Rodiguez-Gallego, Carlos, Boisson, Bertrand, Gallien, Sébastien, Neven, Bénédicte, Michel, Marc, Godeau, Bertrand, Abel, Laurent, Rey, Felix A., Weill, Jean-Claude, Reynaud, Claude-Agnès, Tangye, Stuart G., Casanova, Jean-Laurent, and Mahévas, Matthieu

Abstract

Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)–specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines.

Published
2023
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40. Sensitive visualization of SARS-CoV-2 RNA with CoronaFISH

Author

Elena Rensen, Stefano Pietropaoli, Florian Mueller, Christian Weber, Sylvie Souquere, Sina Sommer, Pierre Isnard, Marion Rabant, Jean-Baptiste Gibier, Fabiola Terzi, Etienne Simon-Loriere, Marie-Anne Rameix-Welti, Gérard Pierron, Giovanna Barba-Spaeth, Christophe Zimmer, Imagerie et Modélisation - Imaging and Modeling, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), National Cystic Fibrosis Reference Center [CHU Necker] (CNR - INSERM U1151), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré [AP-HP], Institut Gustave Roussy (IGR), Virologie Structurale - Structural Virology, E Simon-Loriere acknowledges funding from the French Government’s Investissement d’Avenir program, 'INCEPTION’ (ANR-16-CONV-0005). G Barba-Spaeth acknowledges funding by the Institut Pasteur Coronavirus task force (don AXA COVID-19 project COVID-SPREAD). C Zimmer acknowledges funding by Fondation pour la Recherche Médicale (Equipe FRM, DEQ 20150331762), Institut Carnot Pasteur MS, and Institut Pasteur., We would like to thank Edouard Bertrand, who originally developed smiFISH and Hans Johansson for insightful discussions. We also thank Guillaume Dumenil (Ultrastructural Bioimaging UTechS of Institut Pasteur) for having suggested the application of CoronaFISH to EM and for follow-up discussions. We thank Nathalie Jolly and Nathalie Clément (Center for Translational Science, Institut Pasteur) and Cloé Giquel (Legal department, Institut Pasteur) for their help in obtaining authorization to use patient samples., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Barba Spaeth, Giovanna, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Département Croissance et Signalisation [Paris], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
[SDV]Life Sciences [q-bio], viruses, Health, Toxicology and Mutagenesis, Plant Science, Virus Replication, Antiviral Agents, Sensitivity and Specificity, Biochemistry, Genetics and Molecular Biology (miscellaneous), 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Chlorocebus aethiops, Animals, Humans, Vero Cells, In Situ Hybridization, In Situ Hybridization, Fluorescence, Virus Release, Research Articles, 030304 developmental biology, 0303 health sciences, Alanine, Ecology, SARS-CoV-2, COVID-19, Reproducibility of Results, respiratory system, Adenosine Monophosphate, respiratory tract diseases, COVID-19 Drug Treatment, 3. Good health, [SDV] Life Sciences [q-bio], Microscopy, Electron, RNA, Viral, Caco-2 Cells, 030217 neurology & neurosurgery, Research Article
Abstract

We design an RNA-FISH method to target the plus and minus strands of SARS-CoV-2 RNA, and apply it to image the virus in cell lines, lung tissue, and nasal swabs, by fluorescence and electron microscopy., The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The positive-sense single-stranded RNA virus contains a single linear RNA segment that serves as a template for transcription and replication, leading to the synthesis of positive and negative-stranded viral RNA (vRNA) in infected cells. Tools to visualize vRNA directly in infected cells are critical to analyze the viral replication cycle, screen for therapeutic molecules, or study infections in human tissue. Here, we report the design, validation, and initial application of FISH probes to visualize positive or negative RNA of SARS-CoV-2 (CoronaFISH). We demonstrate sensitive visualization of vRNA in African green monkey and several human cell lines, in patient samples and human tissue. We further demonstrate the adaptation of CoronaFISH probes to electron microscopy. We provide all required oligonucleotide sequences, source code to design the probes, and a detailed protocol. We hope that CoronaFISH will complement existing techniques for research on SARS-CoV-2 biology and COVID-19 pathophysiology, drug screening, and diagnostics.

Published
2022

41. Potential role of invariant NKT cells in the control of pulmonary inflammation and CD8+ T cell response during acute influenza A virus H3N2 pneumonia.

Author

Paget C, Ivanov S, Fontaine J, Blanc F, Pichavant M, Renneson J, Bialecki E, Pothlichet J, Vendeville C, Barba-Spaeth G, Huerre MR, Faveeuw C, Si-Tahar M, and Trottein F

Subjects
Adoptive Transfer, Animals, Antigens, CD, Bronchopneumonia, CD11b Antigen, CD8-Positive T-Lymphocytes metabolism, Dendritic Cells immunology, Enzyme-Linked Immunosorbent Assay, Influenza A Virus, H3N2 Subtype pathogenicity, Integrin alpha Chains, Lung virology, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Orthomyxoviridae Infections pathology, Orthomyxoviridae Infections virology, Pneumonia, Viral pathology, Pneumonia, Viral virology, Polymerase Chain Reaction, Viral Load, CD8-Positive T-Lymphocytes immunology, Inflammation immunology, Influenza A Virus, H3N2 Subtype immunology, Lung immunology, Natural Killer T-Cells immunology, Orthomyxoviridae Infections immunology, Pneumonia, Viral immunology
Abstract

Influenza A virus (IAV) infection results in a highly contagious respiratory illness leading to substantial morbidity and occasionally death. In this report, we assessed the in vivo physiological contribution of invariant NKT (iNKT) lymphocytes, a subset of lipid-reactive αβ T lymphocytes, on the host response and viral pathogenesis using a virulent, mouse-adapted, IAV H3N2 strain. Upon infection with a lethal dose of IAV, iNKT cells become activated in the lungs and bronchoalveolar space to become rapidly anergic to further restimulation. Relative to wild-type animals, C57BL/6 mice deficient in iNKT cells (Jα18(-/-) mice) developed a more severe bronchopneumonia and had an accelerated fatal outcome, a phenomenon reversed by the adoptive transfer of NKT cells prior to infection. The enhanced pathology in Jα18(-/-) animals was not associated with either reduced or delayed viral clearance in the lungs or with a defective local NK cell response. In marked contrast, Jα18(-/-) mice displayed a dramatically reduced IAV-specific CD8(+) T cell response in the lungs and in lung-draining mediastinal lymph nodes. We further show that this defective CD8(+) T cell response correlates with an altered accumulation and maturation of pulmonary CD103(+), but not CD11b(high), dendritic cells in the mediastinal lymph nodes. Taken together, these findings point to a role for iNKT cells in the control of pneumonia as well as in the development of the CD8(+) T cell response during the early stage of acute IAV H3N2 infection.

Published
2011
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42. Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics.

Author

Marcello T, Grakoui A, Barba-Spaeth G, Machlin ES, Kotenko SV, MacDonald MR, and Rice CM

Subjects
Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular virology, Cell Line, Tumor, Dose-Response Relationship, Drug, Humans, Interferons, Liver Neoplasms pathology, Liver Neoplasms virology, Oligonucleotide Array Sequence Analysis, RNA, Viral genetics, Antiviral Agents pharmacology, Cytokines pharmacology, Gene Expression Regulation, Viral drug effects, Hepacivirus genetics, Interferon-alpha pharmacology, Interleukins pharmacology, Signal Transduction drug effects, Virus Replication drug effects
Abstract

Background & Aims: Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. Current therapy with pegylated interferon alpha (IFN-alpha) in combination with ribavirin is associated with adverse effects and often fails to induce a sustained response. IFN-lambdas, recently discovered IFN gene family members, exhibit antiviral and cell stimulatory activities similar to IFN-alpha. We aimed to determine whether IFN-lambda exhibits antiviral activity toward HCV and to compare the signal transduction and effector gene pathways with those of IFN-alpha., Methods: Using the HCV replicon system and cell culture infectious reporter virus, we compared IFN-alpha and IFN-lambda effects on HCV RNA replication and protein expression, as measured by quantitative reverse-transcriptase polymerase chain reaction, luciferase expression, and Western blot. Receptor expression and signaling pathways were explored using flow cytometry and Western blot. IFN-alpha- and IFN-lambda-mediated gene expression changes were compared using microarray analyses., Results: IFN-lambda exhibited dose- and time-dependent HCV inhibition, independent of types I and II IFN receptors. The kinetics of IFN-lambda-mediated signal transducers and activators of transcription (STAT) activation and induction of potential effector genes were distinct from those of IFN-alpha. IFN-lambda induced steady increases in levels of known interferon stimulated genes (ISGs), whereas IFN-alpha ISGs peaked early and declined rapidly. IFN-lambda inhibited replication of HCV genotypes 1 and 2 and enhanced the antiviral efficacy of subsaturating levels of IFN-alpha., Conclusions: These results demonstrate distinct differences in IFN-lambda- and IFN-alpha-induced antiviral states. Understanding these differences may prove useful for developing new HCV treatment strategies.

Published
2006
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