316 results on '"Kuhn, JH"'
Search Results
2. Local, national, and regional viral haemorrhagic fever pandemic potential in Africa: a multistage analysis
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Pigott, DM, Deshpande, A, Letourneau, I, Morozoff, C, Reiner, RC, Kraemer, MUG, Brent, SE, Bogoch, II, Khan, K, Biehl, MH, Burstein, R, Earl, L, Fullman, N, Messina, JP, Mylne, AQN, Moyes, CL, Shearer, FM, Bhatt, S, Brady, OJ, Gething, PW, Weiss, DJ, Tatem, AJ, Caley, L, De Groeve, T, Vernaccini, L, Golding, N, Horby, P, Kuhn, JH, Laney, SJ, Ng, E, Piot, P, Sankoh, O, Murray, CJL, Hay, SI, and Medical Research Council (MRC)
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EMERGING INFECTIOUS-DISEASES ,Science & Technology ,Hemorrhagic Fevers, Viral ,PREDICTION ,MODELS ,EBOLA ,SCIENCE ,11 Medical And Health Sciences ,Risk Assessment ,Article ,Disease Outbreaks ,Medicine, General & Internal ,General & Internal Medicine ,Africa ,Humans ,ZOONOTIC NICHE ,Hemorrhagic Fever, Crimean ,LASSA FEVER ,HEALTH ,VIRUS-DISEASE ,REFORMS ,Epidemics ,Life Sciences & Biomedicine ,Pandemics - Abstract
Summary Background Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean–Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease. Methods In this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally. Findings We found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels. Interpretation Our analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support. Funding Paul G Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development.
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- 2017
3. Taxonomy of prokaryotic viruses: 2017 update from the ICTV Bacterial and Archaeal Viruses Subcommittee
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Adriaenssens, EM, Wittmann, J, Kuhn, JH, Turner, D, Sullivan, MB, Dutilh, BE, Jang, HB, van Zyl, LJ, Klumpp, J, Lobocka, M, Moreno Switt, AI, Rumnieks, J, Edwards, RA, Uchiyama, J, Alfenas-Zerbini, P, Petty, NK, Kropinski, AM, Barylski, J, Gillis, A, Clokie, MRC, Prangishvili, D, Lavigne, R, Aziz, RK, Duffy, S, Krupovic, M, Poranen, MM, Knezevic, P, Enault, F, Tong, Y, Oksanen, HM, Rodney Brister, J, Adriaenssens, EM, Wittmann, J, Kuhn, JH, Turner, D, Sullivan, MB, Dutilh, BE, Jang, HB, van Zyl, LJ, Klumpp, J, Lobocka, M, Moreno Switt, AI, Rumnieks, J, Edwards, RA, Uchiyama, J, Alfenas-Zerbini, P, Petty, NK, Kropinski, AM, Barylski, J, Gillis, A, Clokie, MRC, Prangishvili, D, Lavigne, R, Aziz, RK, Duffy, S, Krupovic, M, Poranen, MM, Knezevic, P, Enault, F, Tong, Y, Oksanen, HM, and Rodney Brister, J
- Published
- 2018
4. TESLA Technical Design Report Part III: Physics at an e+e- Linear Collider
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Heuer, RD, Miller, DJ, Richard, F, Zerwas, PM, Aguilar Saavedra, JA, Alcaraz, J, Ali, A, Ambrosanio, S, Andreazza, A, Andruszkow, J, Badelek, B, Ballestrero, A, Barklow, T, Bartl, A, Battaglia, M, Behnke, T, Belanger, Genevieve, Benson, D, Berggren, M, Bernreuther, W, Besancon, M, Biebel, J, Biebel, O, Bigi, I, Van der Bij, JJ, Binoth, T, Blair, GA, Blochinger, C, Blumlein, J, Boonekamp, M, Boos, E, Borissov, G, Brandenburg, A, Brient, JC, Bruni, G, Busser, K, Burrows, P, Casalbuoni, R, Castanier, C, Chankowski, P, Chekanov, A, Chierici, R, Choi, SY, Christova, P, Ciafaloni, P, Comelli, D, Conteras, G, Danilov, M, Da Silva, W, Deandrea, A, De Boer, W, De Curtis, S, De Jong, SJ, Denner, A, De Roeck, A, Desch, K, De Wolf, E, Dittmaier, S, Djordjadze, V, Djouadi, A, Dominici, D, Doncheski, M, Dova, MT, Drollinger, V, Eberl, H, Erler, J, Eskreys, A, Espinosa, JR, Evanson, N, Fernandez, E, Forshaw, J, Fraas, H, Franke, F, Freitas, A, Gangemi, F, Garcia-Abia, P, Gatto, R, Gay, P, Gehrmann, T, Ridder, Gehrmann De A, Gensch, U, Ghodbane, N, Ginzburg, IF, Godbole, R, Godfrey, S, Gounaris, G, Grazzini, M, Gross, E, Grzadkowski, B, Guasch, J, Gunion, JF, Hagiwara, K, Han, T, Harder, K, Harlander, R, Hawkings, R, Heinemeyer, S, Hesselbach, S, Heusch, CA, Hewett, J, Hiller, G, Hoang, A, Hollik, W, Illana, JI, Ilyin, VA, Indumathi, D, Ishihara, S, Jack, M, Jadach, S, Jegerlehner, F, Jezabek, M, Jikia, G, Jonsson, L, Jankowski, P, Jurkiewicz, P, Juste, A, Kagan, A, Kalinowski, J, Kalmykov, M, Kalyniak, P, Kamal, B, Kamoshita, J, Kanemura, S, Kapusta, F, Katsanevas, S, Keranen, R, Khoze, V, Kiiskinen, A, Kilian, W, Klasen, M, Kneur, JL, Kniehl, BA, Kobel, M, Kolodziej, K, Kramer, M, Kraml, S, Krawczyk, M, Kuhn, JH, Kwiecinski, J, Laurelli, P, Leike, A, Letts, J, Lohmann, W, Lola, S, Lutz, P, Mattig, P, Majerotto, W, Mannel, T, Martinez, M, Martyn, HU, Mayer, T, Mele, B, Melles, M, Menges, W, Merino, G, Meyer, N, Minkowski, P, Miquel, R, Monig, K, Montagna, G, Moortgat-Pick, G, De Freitas, Mora P, Moreau, G, Moretti, M, Moretti, S, Motyka, L, Moultaka, G, Muhlleitner, M, Nauenberg, U, Nisius, R, Nowak, H, Ohl, T, Orava, R, Orloff, J, Osland, P, Pancheri, G, Pankov, AA, Papadopoulos, C, Paver, N, Peralta, D, Phillips, HT, Picinini, F, Placzek, W, Pohl, M, Porod, W, Pukhov, A, Raspereza, A, Reid, D, Riemann, S, Riemann, T, Rosati, S, Roth, M, Roth, S, Royon, C, Ruckl, R, Ruiz-Morales, E, Sachwitz, M, Schieck, J, Schreiber, HJ, Schulte, D, Schumacher, M, Settles, RD, Seymour, M, Shanidze, R, Sjostrand, T, Skrzypek, M, Soldner-Rembold, S, Sopczak, A, Spiesberger, H, Spira, M, Steiner, H, Stratmann, M, Sumino, Y, Tapprogge, S, Telnov, V, Teubner, T, Tonazzo, A, Troncon, C, Veretin, O, Verzegnassi, C, Vest, A, Vicini, A, Videau, H, Vogelsang, W, Vogt, A, Vogt, H, Wackeroth, D, Wagner, A, Wallon, S, Weiglein, G, Weinzierl, S, Wengler, T, Wermes, N, Werthenbach, A, Wilson, G, Winter, M, Zarnecki, AF, Ziaja, B, and Zochowski, J
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Physics::Instrumentation and Detectors ,Physics::Medical Physics ,Computer Science::Mathematical Software ,Physics::Accelerator Physics ,Centre for Theoretical Studies (Ceased to exist at the end of 2003) ,High Energy Physics::Experiment ,Centre for Theoretical Studies - Abstract
The TESLA Technical Design Report Part III: Physics at an e+e- Linear Collider
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- 2001
5. A proposal to change existing virus species names to non-Latinized binomials
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van Regenmortel, MHV, Burke, DS, Calisher, CH, Dietzgen, RG, Fauquet, CM, Ghabrial, SA, Jahrling, PB, Johnson, KM, Holbrook, MR, Horzinek, MC, Keil, GM, Kuhn, JH, Mahy, BWJ, Martelli, GP, Pringle, C, Rybicki, EP, Skern, T, Tesh, RB, Wahl-Jensen, V, Walker, PJ, Weaver, SC, van Regenmortel, MHV, Burke, DS, Calisher, CH, Dietzgen, RG, Fauquet, CM, Ghabrial, SA, Jahrling, PB, Johnson, KM, Holbrook, MR, Horzinek, MC, Keil, GM, Kuhn, JH, Mahy, BWJ, Martelli, GP, Pringle, C, Rybicki, EP, Skern, T, Tesh, RB, Wahl-Jensen, V, Walker, PJ, and Weaver, SC
- Abstract
A proposal has been posted on the ICTV website (2011. 001aG. N. v1. binomial_sp_names) to replace virus species names by non-Latinized binomial names consisting of the current italicized species name with the terminal word "virus" replaced by the italicized and non-capitalized genus name to which the species belongs. If implemented, the current italicized species name Measles virus, for instance, would become Measles morbillivirus while the current virus name measles virus and its abbreviation MeV would remain unchanged. The rationale for the proposed change is presented. © 2010 Springer-Verlag.
- Published
- 2010
6. Safety and immunogenicity of a delayed booster dose of the rVSVΔG-ZEBOV-GP vaccine for prevention of Ebola virus disease: a multicentre, open-label, phase 2 randomised controlled trial.
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Davey RT Jr, Collins GL, Rouphael N, Poliquin G, McConnell R, Grubbs G, Moir SL, Langley JM, Teitelbaum M, Hewlett AL, McLellan SLF, Bhadelia N, Raabe VN, Mulligan MJ, Maljkovic Berry I, Dighero-Kemp B, Kurtz JR, Hensley LE, Dozier NCE, Marron LCB, DuChene A, Kuhn JH, Brown SK, Khurana S, Lane HC, and Neaton JD
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Background: rVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation., Methods: In this open-label phase 2 randomised controlled trial, we compared antibody titres at month 36 in participants who had received a homologous booster dose at month 18 following primary immunisation with those who had received no booster. From Oct 25, 2016, to Jan 29, 2020, healthy adults aged 18 years or older deemed at occupational risk of exposure to Ebola virus due to laboratory work, clinical duties, or travel to an active endemic region were recruited from four hospital clinics in the USA and one hospital clinic in Canada and received primary vaccination with 2×10
7 plaque-forming unit per mL of VSVΔG-ZEBOV-GP. 18 months later, individuals who consented and were still eligible were randomly assigned 1:1 to receive either a homologous booster dose or no booster. Study visits for safety and serial blood collections for antibody titres were done on enrolled participants at months 0, 1, 3, 6, 12, 18, 19, 24, 30, and 36. Through July, 2021, a web-based application was used for randomisation, including assignments with schedules for each of the five sites using mixed permuted blocks. The trial was not masked to participants or site staff. The primary endpoint was a comparison of geometric mean titres (GMTs) of anti-Ebola virus glycoprotein IgG antibody at month 36 (ie, 18 months after randomisation) for all randomly assigned participants who completed the 36 months of follow-up (primary analysis cohort). Investigators were aware of antibody titres from baseline (enrolment) through month 18 but were masked to summary data by randomisation group after month 18. This study is registered with ClinicalTrials.gov (NCT02788227)., Findings: Of the 248 participants who enrolled and received their primary immunisation, 114 proceeded to the randomisation step at month 18. The two randomisation groups were balanced: 57 participants (24 [42%] of whom were female; median age was 42 years [IQR 35-50]) were randomly assigned to the booster group and 57 (24 [42%] of whom were female; median age was 42 years [IQR 36-51]) to the no-booster group. Of those randomly assigned, 92 participants (45 in the booster group and 47 in the no-booster group) completed 36 months of follow-up. At 18 months after primary immunisation, GMTs in the no-booster group increased from a baseline of 10 ELISA units (EU)/mL (95% CI 7-14) to 1451 EU/mL (1118-1882); GMTs in the booster group increased from 9 EU/mL (6-16) to 1769 EU/mL (1348-2321). At month 19, GMTs were 31 408 EU/mL (23 181-42 554) for the booster group and 1406 EU/mL (1078-1833) for the no-booster group; at month 36, GMTs were 10 146 EU/mL (7960-12 933) for the booster group and 1240 EU/mL (984-1563) for the no-booster group. Accordingly, the geometric mean ratio (GMR) of antibody titres had increased almost 21-fold more in the booster versus no-booster group at 1 month after booster administration (GMR 20·6; 95% CI 18·2-23·0; p<0·0001) and was still over 7-fold higher at month 36 (GMR 7·8; 95% CI 5·5-10·2; p<0·0001). Consistent with previous reports of this vaccine's side-effects, transient mono-articular or oligo-articular arthritis was diagnosed in 18 (9%) of 207 primary vaccination recipients; after randomisation, arthritis was diagnosed in one (2%) of 57 participants in the no-booster group. No new cases of arthritis developed after booster administration. Four serious adverse events occurred following randomisation: one (epistaxis) in the booster group and three (gastrointestinal haemorrhage, prostate cancer, and tachyarrhythmia) in the no-booster group. None of the serious adverse events was judged attributable to the booster vaccination assignment., Interpretation: In addition to no new safety concerns and in marked contrast to earlier trials evaluating short-term boosting, delaying a rVSVΔG-ZEBOV-GP booster until month 18 resulted in an increase in GMT that remained several-fold above the no-booster group GMT for at least 18 months. These findings could have implications for defining the optimal timing of booster doses as pre-exposure prophylaxis in populations at ongoing risk for Ebola virus exposure., Funding: The Division of Intramural Research and the Division of Clinical Research of the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health, Canadian Immunization Research Network through the Public Health Agency of Canada, Canadian Institutes of Health Research, and the US Defense Threat Reduction Agency., Competing Interests: Declaration of interests We declare no competing interests., (Published by Elsevier Ltd.)- Published
- 2024
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7. The polinton-like supergroup of viruses: evolution, molecular biology, and taxonomy.
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Koonin EV, Fischer MG, Kuhn JH, and Krupovic M
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- DNA Transposable Elements genetics, Capsid Proteins genetics, Capsid Proteins metabolism, Animals, DNA Viruses genetics, DNA Viruses classification, Virophages genetics, Virophages classification, Viral Proteins genetics, Viral Proteins metabolism, Giant Viruses genetics, Giant Viruses classification, Eukaryota virology, Eukaryota genetics, Phylogeny, Evolution, Molecular, Genome, Viral genetics
- Abstract
SUMMARYPolintons are 15-20 kb-long self-synthesizing transposons that are widespread in eukaryotic, and in particular protist, genomes. Apart from a transposase and a protein-primed DNA polymerase, polintons encode homologs of major and minor jelly-roll capsid proteins, DNA-packaging ATPases, and proteases involved in capsid maturation of diverse eukaryotic viruses of kingdom Bamfordvirae . Given the conservation of these structural and morphogenetic proteins among polintons, these elements are predicted to alternate between transposon and viral lifestyles and, although virions have thus far not been detected, are classified as viruses (class Polintoviricetes ) in the phylum Preplasmiviricota . Related to polintoviricetes are vertebrate adenovirids; unclassified polinton-like viruses (PLVs) identified in various environments or integrated into diverse protist genomes; virophages ( Maveriviricetes ), which are part of tripartite hyperparasitic systems including protist hosts and giant viruses; and capsid-less derivatives, such as cytoplasmic linear DNA plasmids of fungi and transpovirons. Phylogenomic analysis indicates that the polinton-like supergroup of viruses bridges bacterial tectivirids (preplasmiviricot class Tectiliviricetes ) to the phylum Nucleocytoviricota that includes large and giant eukaryotic DNA viruses. Comparative structural analysis of proteins encoded by polinton-like viruses led to the discovery of previously undetected functional domains, such as terminal proteins and distinct proteases implicated in DNA polymerase processing, and clarified the evolutionary relationships within Polintoviricetes . Here, we leverage these insights into the evolution of the polinton-like supergroup to develop an amended megataxonomy that groups Polintoviricetes , PLVs (new class ' Aquintoviricetes '), and virophages (renamed class ' Virophaviricetes ') together with Adenoviridae (new class ' Pharingeaviricetes ') in a preplasmiviricot subphylum ' Polisuviricotina ' sister to a subphylum including Tectiliviricetes (' Prepoliviricotina ')., Competing Interests: The authors declare no conflict of interest.
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- 2024
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8. Promotion of order Bunyavirales to class Bunyaviricetes to accommodate a rapidly increasing number of related polyploviricotine viruses.
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Kuhn JH, Brown K, Adkins S, de la Torre JC, Digiaro M, Ergünay K, Firth AE, Hughes HR, Junglen S, Lambert AJ, Maes P, Marklewitz M, Palacios G, Sasaya T, Shi M, Zhang Y-Z, Wolf YI, and Turina M
- Abstract
Prior to 2017, the family Bunyaviridae included five genera of arthropod and rodent viruses with tri-segmented negative-sense RNA genomes related to the Bunyamwera virus. In 2017, the International Committee on Taxonomy of Viruses (ICTV) promoted the family to order Bunyavirales and subsequently greatly expanded its composition by adding multiple families for non-segmented to polysegmented viruses of animals, fungi, plants, and protists. The continued and accelerated discovery of bunyavirals highlighted that an order would not suffice to depict the evolutionary relationships of these viruses. Thus, in April 2024, the order was promoted to class Bunyaviricetes . This class currently includes two major orders, Elliovirales ( Cruliviridae , Fimoviridae , Hantaviridae , Peribunyaviridae , Phasmaviridae , Tospoviridae , and Tulasviridae ) and Hareavirales ( Arenaviridae , Discoviridae , Konkoviridae , Leishbuviridae , Mypoviridae , Nairoviridae , Phenuiviridae , and Wupedeviridae ), for hundreds of viruses, many of which are pathogenic for humans and other animals, plants, and fungi.
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- 2024
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9. Global remodeling of ADP-ribosylation by PARP1 suppresses influenza A virus infection.
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Zhang Z, Uribe I, Davis KA, McPherson RL, Larson GP, Badiee M, Tran V, Ledwith MP, Feltman E, Yú S, Caì Y, Chang CY, Yang X, Ma Z, Chang P, Kuhn JH, Leung AKL, and Mehle A
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ADP-ribosylation is a highly dynamic and fully reversible post-translational modification performed by poly(ADP-ribose) polymerases (PARPs) that modulates protein function, abundance, localization and turnover. Here we show that influenza A virus infection causes a rapid and dramatic upregulation of global ADP-ribosylation that inhibits viral replication. Mass spectrometry defined for the first time the global ADP-ribosylome during infection, creating an infection-specific profile with almost 4,300 modification sites on ∼1,080 host proteins, as well as over 100 modification sites on viral proteins. Our data indicate that the global increase likely reflects a change in the form of ADP-ribosylation rather than modification of new targets. Functional assays demonstrated that modification of the viral replication machinery antagonizes its activity and further revealed that the anti-viral activity of PARPs and ADP-ribosylation is counteracted by the influenza A virus protein NS1, assigning a new activity to the primary viral antagonist of innate immunity. We identified PARP1 as the enzyme producing the majority of poly(ADP-ribose) present during infection. Influenza A virus replicated faster in cells lacking PARP1, linking PARP1 and ADP-ribosylation to the anti-viral phenotype. Together, these data establish ADP-ribosylation as an anti-viral innate immune-like response to viral infection antagonized by a previously unknown activity of NS1.
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- 2024
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10. Ambiviricota , a novel ribovirian phylum for viruses with viroid-like properties.
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Kuhn JH, Botella L, de la Peña M, Vainio EJ, Krupovic M, Lee BD, Navarro B, Sabanadzovic S, Simmonds P, and Turina M
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- Phylogeny, RNA, Viral genetics, RNA Viruses genetics, RNA Viruses classification, Fungi genetics, Fungi virology, RNA-Dependent RNA Polymerase genetics, Fungal Viruses genetics, Fungal Viruses classification, Fungal Viruses isolation & purification, Genome, Viral, Open Reading Frames, Viroids genetics, Viroids classification
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Fungi harbor a vast diversity of mobile genetic elements (MGEs). Recently, novel fungal MGEs, tentatively referred to as 'ambiviruses,' were described. 'Ambiviruses' have single-stranded RNA genomes of about 4-5 kb in length that contain at least two open reading frames (ORFs) in non-overlapping ambisense orientation. Both ORFs are conserved among all currently known 'ambiviruses,' and one of them encodes a distinct viral RNA-directed RNA polymerase (RdRP), the hallmark gene of ribovirian kingdom Orthornavirae . However, 'ambivirus' genomes are circular and predicted to replicate via a rolling-circle mechanism. Their genomes are also predicted to form rod-like structures and contain ribozymes in various combinations in both sense and antisense orientations-features reminiscent of viroids, virusoids, ribozyvirian kolmiovirids, and yet-unclassified MGEs (such as 'epsilonviruses,' 'zetaviruses,' and some 'obelisks'). As a first step toward the formal classification of 'ambiviruses,' the International Committee on Taxonomy of Viruses (ICTV) recently approved the establishment of a novel ribovirian phylum, Ambiviricota , to accommodate an initial set of 20 members with well-annotated genome sequences., Competing Interests: The authors declare no conflict of interest.
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- 2024
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11. ICTV Virus Taxonomy Profile: Phasmaviridae 2024.
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Kuhn JH and Hughes HR
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- Animals, Negative-Sense RNA Viruses genetics, Negative-Sense RNA Viruses classification, Virion genetics, Viral Proteins genetics, Viral Proteins metabolism, Insecta virology, Phylogeny, Virus Replication, Genome, Viral, RNA, Viral genetics
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Phasmaviridae is a family for negative-sense RNA viruses with genomes of about 9.7-15.8 kb. These viruses are maintained in and/or transmitted by insects. Phasmavirids produce enveloped virions containing three single-stranded RNA segments that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Phasmaviridae, which is available at ictv.global/report/phasmaviridae.
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- 2024
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12. Natural history of eukaryotic DNA viruses with double jelly-roll major capsid proteins.
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Krupovic M, Kuhn JH, Fischer MG, and Koonin EV
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- Eukaryota virology, Eukaryota genetics, DNA-Directed DNA Polymerase metabolism, DNA-Directed DNA Polymerase chemistry, DNA-Directed DNA Polymerase genetics, Models, Molecular, Phylogeny, Capsid Proteins metabolism, Capsid Proteins chemistry, Capsid Proteins genetics, DNA Viruses genetics
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The phylum Preplasmiviricota (kingdom Bamfordvirae , realm Varidnaviria ) is a broad assemblage of diverse viruses with comparatively short double-stranded DNA genomes (<50 kbp) that produce icosahedral capsids built from double jelly-roll major capsid proteins. Preplasmiviricots infect hosts from all cellular domains, testifying to their ancient origin, and, in particular, are associated with six of the seven supergroups of eukaryotes. Preplasmiviricots comprise four major groups of viruses, namely, polintons, polinton-like viruses (PLVs), virophages, and adenovirids. We used protein structure modeling and analysis to show that protein-primed DNA polymerases (pPolBs) of polintons, virophages, and cytoplasmic linear plasmids encompass an N-terminal domain homologous to the terminal proteins (TPs) of prokaryotic PRD1-like tectivirids and eukaryotic adenovirids that are involved in protein-primed replication initiation, followed by a viral ovarian tumor-like cysteine deubiquitinylase (vOTU) domain. The vOTU domain is likely responsible for the cleavage of the TP from the large pPolB polypeptide and is inactivated in adenovirids, in which TP is a separate protein. Many PLVs and transpovirons encode a distinct derivative of polinton-like pPolB that retains the TP, vOTU, and pPolB polymerization palm domains but lacks the exonuclease domain and instead contains a superfamily 1 helicase domain. Analysis of the presence/absence and inactivation of the vOTU domains and replacement of pPolB with other DNA polymerases in eukaryotic preplasmiviricots enabled us to outline a complete scenario for their origin and evolution., Competing Interests: Competing interests statement:The authors declare no competing interest.
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- 2024
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13. First Decade of Supportive Services for Veteran Families Program and Homelessness, 2012-2022.
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Wilkinson R, Byrne T, Cowden RG, Long KNG, Kuhn JH, Koh HK, and Tsai J
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- Humans, United States, Family, Social Support, Ill-Housed Persons, United States Department of Veterans Affairs organization & administration, Veterans
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As homelessness remains an urgent public health crisis in the United States, specific programs in the US Department of Veterans Affairs (VA) system may serve as a roadmap for addressing it. We examine lessons learned from the first decade (2012-2022) of the Supportive Services for Veteran Families (SSVF) program, a cornerstone in the VA continuum of homeless services aimed at both preventing homelessness among those at risk and providing rapid rehousing for veterans and their families who are currently experiencing homelessness. Drawing on information from annual reports and other relevant literature, we have identified 3 themes of SSVF that emerged as features to comprehensively deliver support for homeless veterans and their families: (1) responsiveness and flexibility, (2) coordination and integration, and (3) social resource engagement. Using these strategies, SSVF reached nearly three quarters of a million veterans and their families in its first decade, thereby becoming one of the VA's most substantial programmatic efforts designed to address homelessness. We discuss how each feature might apply to addressing homelessness in the general population as well as future research directions. ( Am J Public Health . 2024;114(6):610-618. https://doi.org/10.2105/AJPH.2024.307625).
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- 2024
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14. Treatment of highly virulent mammarenavirus infections-status quo and future directions.
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Nuñez IA, Crane A, Crozier I, Worwa G, and Kuhn JH
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- Humans, Animals, Virulence, Drug Design, Antiviral Agents pharmacology, Drug Development, Arenaviridae Infections drug therapy, Arenaviridae Infections virology, Arenaviridae drug effects
- Abstract
Introduction: Mammarenaviruses are negative-sense bisegmented enveloped RNA viruses that are endemic in Africa, the Americas, and Europe. Several are highly virulent, causing acute human diseases associated with high case fatality rates, and are considered to be significant with respect to public health impact or bioterrorism threat., Areas Covered: This review summarizes the status quo of treatment development, starting with drugs that are in advanced stages of evaluation in early clinical trials, followed by promising candidate medical countermeasures emerging from bench analyses and investigational animal research., Expert Opinion: Specific therapeutic treatments for diseases caused by mammarenaviruses remain limited to the off-label use of ribavirin and transfusion of convalescent sera. Progress in identifying novel candidate medical countermeasures against mammarenavirus infection has been slow in part because of the biosafety and biosecurity requirements. However, novel methodologies and tools have enabled increasingly efficient high-throughput molecular screens of regulatory-agency-approved small-molecule drugs and led to the identification of several compounds that could be repurposed for the treatment of infection with several mammarenaviruses. Unfortunately, most of them have not yet been evaluated in vivo . The most promising treatment under development is a monoclonal antibody cocktail that is protective against multiple lineages of the Lassa virus in nonhuman primate disease models.
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- 2024
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15. Monkeypox virus genomic accordion strategies.
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Monzón S, Varona S, Negredo A, Vidal-Freire S, Patiño-Galindo JA, Ferressini-Gerpe N, Zaballos A, Orviz E, Ayerdi O, Muñoz-Gómez A, Delgado-Iribarren A, Estrada V, García C, Molero F, Sánchez-Mora P, Torres M, Vázquez A, Galán JC, Torres I, Causse Del Río M, Merino-Diaz L, López M, Galar A, Cardeñoso L, Gutiérrez A, Loras C, Escribano I, Alvarez-Argüelles ME, Del Río L, Simón M, Meléndez MA, Camacho J, Herrero L, Jiménez P, Navarro-Rico ML, Jado I, Giannetti E, Kuhn JH, Sanchez-Lockhart M, Di Paola N, Kugelman JR, Guerra S, García-Sastre A, Cuesta I, Sánchez-Seco MP, and Palacios G
- Subjects
- Humans, Monkeypox virus genetics, Genomics, Orthopoxvirus, Mpox (monkeypox) genetics, Poxviridae
- Abstract
The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability., (© 2024. The Author(s).)
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- 2024
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16. ICTV Virus Taxonomy Profile: Hantaviridae 2024.
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Bradfute SB, Calisher CH, Klempa B, Klingström J, Kuhn JH, Laenen L, Tischler ND, and Maes P
- Subjects
- Animals, Humans, Negative-Sense RNA Viruses, Virion genetics, Nucleoproteins, Open Reading Frames, Mammals, RNA Viruses
- Abstract
Hantaviridae is a family for negative-sense RNA viruses with genomes of about 10.5-14.6 kb. These viruses are maintained in and/or transmitted by fish, reptiles, and mammals. Several orthohantaviruses can infect humans, causing mild, severe, and sometimes-fatal diseases. Hantavirids produce enveloped virions containing three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hantaviridae, which is available at ictv.global/report/hantaviridae.
- Published
- 2024
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17. Isolation of Diverse Simian Arteriviruses Causing Hemorrhagic Disease.
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Shaw TM, Dettle ST, Mejia A, Hayes JM, Simmons HA, Basu P, Kuhn JH, Ramuta MD, Warren CJ, Jahrling PB, O'Connor DH, Huang L, Zaeem M, Seo J, Slukvin II, Brown ME, and Bailey AL
- Subjects
- Animals, Mice, Macaca, Macrophages, Cell Line, Arterivirus genetics
- Abstract
Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+-enriched hematopoietic stem cells. The combined effort resulted in successful virus isolation; however, no single approach was successful for all 4 simarteriviruses. We describe several approaches that might be used to isolate additional simarteriviruses for phenotypic characterization. Our results will expedite laboratory studies of simarteriviruses to elucidate virus-host interactions, assess zoonotic risk, and develop medical countermeasures.
- Published
- 2024
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18. ICTV Virus Taxonomy Profile: Nairoviridae 2024.
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Kuhn JH, Alkhovsky SV, Avšič-Županc T, Bergeron É, Burt F, Ergünay K, Garrison AR, Marklewitz M, Mirazimi A, Papa A, Pawęska JT, Spengler JR, and Palacios G
- Subjects
- Animals, Humans, Open Reading Frames, Viral Proteins genetics, Nairovirus genetics, Nairovirus classification, Nairovirus isolation & purification, RNA, Viral genetics, Phylogeny, Virion ultrastructure, RNA-Dependent RNA Polymerase genetics, Genome, Viral
- Abstract
Nairoviridae is a family for negative-sense RNA viruses with genomes of about 17.2-21.1 kb. These viruses are maintained in and/or transmitted by arthropods among birds, reptiles and mammals. Norwaviruses and orthonairoviruses can cause febrile illness in humans. Several orthonairoviruses can infect mammals, causing mild, severe and sometimes, fatal diseases. Nairovirids produce enveloped virions containing two or three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), sometimes a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Nairoviridae , which is available at www.ictv.global/report/nairoviridae.
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- 2024
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19. Polyubiquitylated rice stripe virus NS3 translocates to the nucleus to promote cytosolic virus replication via miRNA-induced fibrillin 2 upregulation.
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Zhang L, Li Y, Kuhn JH, Zhang K, Song Q, and Liu F
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- Animals, Up-Regulation, Fibrillin-2 genetics, Fibrillin-2 metabolism, Virus Replication, Plant Diseases, MicroRNAs genetics, MicroRNAs metabolism, Tenuivirus metabolism, Oryza genetics, Hemiptera
- Abstract
Viruses are encapsidated mobile genetic elements that rely on host cells for replication. Several cytoplasmic RNA viruses synthesize proteins and/or RNAs that translocate to infected cell nuclei. However, the underlying mechanisms and role(s) of cytoplasmic-nuclear trafficking are unclear. We demonstrate that infection of small brown planthoppers with rice stripe virus (RSV), a negarnaviricot RNA virus, results in K63-linked polyubiquitylation of RSV's nonstructural protein 3 (NS3) at residue K127 by the RING ubiquitin ligase (E3) LsRING. In turn, ubiquitylation leads to NS3 trafficking from the cytoplasm to the nucleus, where NS3 regulates primary miRNA pri-miR-92 processing through manipulation of the microprocessor complex, resulting in accumulation of upregulated miRNA lst-miR-92. We show that lst-miR-92 regulates the expression of fibrillin 2, an extracellular matrix protein, thereby increasing RSV loads. Our results highlight the manipulation of intranuclear, cytoplasmic, and extracellular components by an RNA virus to promote its own replication in an insect vector., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
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- 2024
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20. Virome profiling of fig wasps (Ceratosolen spp.) reveals virus diversity spanning four realms.
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Adhikari BN, Paskey AC, Frey KG, Bennett AJ, Long KA, Kuhn JH, Hamilton T, Glang L, Cer RZ, Goldberg TL, and Bishop-Lilly KA
- Subjects
- Humans, Animals, Virome, Pollination, Fruit, Symbiosis, Wasps, Ficus
- Abstract
We investigated the virome of agaonid fig wasps (Ceratosolen spp.) inside syconia ("fruits") of various Ficus trees fed upon by frugivores such as pteropodid bats in Sub-Saharan Africa. This virome includes representatives of viral families spanning four realms and includes near-complete genome sequences of three novel viruses and fragments of five additional potentially novel viruses evolutionarily associated with insects, fungi, plants, and vertebrates. Our study provides evidence that frugivorous animals are exposed to a plethora of viruses by coincidental consumption of fig wasps, which are obligate pollinators of figs worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)
- Published
- 2024
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21. ICTV Virus Taxonomy Profile: Kolmioviridae 2024.
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Kuhn JH, Babaian A, Bergner LM, Dény P, Glebe D, Horie M, Koonin EV, Krupovic M, Paraskevopoulou S, de la Peña M, Smura T, and Hepojoki J
- Subjects
- Animals, Humans, Biological Evolution, Negative-Sense RNA Viruses, RNA Polymerase II, Mammals, Helper Viruses, Viroids
- Abstract
Kolmioviridae is a family for negative-sense RNA viruses with circular, viroid-like genomes of about 1.5-1.7 kb that are maintained in mammals, amphibians, birds, fish, insects and reptiles. Deltaviruses, for instance, can cause severe hepatitis in humans. Kolmiovirids encode delta antigen (DAg) and replicate using host-cell DNA-directed RNA polymerase II and ribozymes encoded in their genome and antigenome. They require evolutionary unrelated helper viruses to provide envelopes and incorporate helper virus proteins for infectious particle formation. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Kolmioviridae , which is available at ictv.global/report/kolmioviridae.
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- 2024
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22. ICTV Virus Taxonomy Profile: Filoviridae 2024.
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Biedenkopf N, Bukreyev A, Chandran K, Di Paola N, Formenty PBH, Griffiths A, Hume AJ, Mühlberger E, Netesov SV, Palacios G, Pawęska JT, Smither S, Takada A, Wahl V, and Kuhn JH
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- Animals, Humans, Phylogeny, Genome, Viral, Virus Replication, Mammals genetics, Ebolavirus genetics, Rhabdoviridae genetics, Marburgvirus
- Abstract
Filoviridae is a family of negative-sense RNA viruses with genomes of about 13.1-20.9 kb that infect fish, mammals and reptiles. The filovirid genome is a linear, non-segmented RNA with five canonical open reading frames (ORFs) that encode a nucleoprotein (NP), a polymerase cofactor (VP35), a glycoprotein (GP
1,2 ), a transcriptional activator (VP30) and a large protein (L) containing an RNA-directed RNA polymerase (RdRP) domain. All filovirid genomes encode additional proteins that vary among genera. Several filovirids (e.g., Ebola virus, Marburg virus) are pathogenic for humans and highly virulent. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Filoviridae , which is available at www.ictv.global/report/filoviridae.- Published
- 2024
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23. Megataxonomy and global ecology of the virosphere.
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Koonin EV, Kuhn JH, Dolja VV, and Krupovic M
- Subjects
- Metagenomics methods, Ecology, Phylogeny, Genome, Viral, Viruses genetics
- Abstract
Nearly all organisms are hosts to multiple viruses that collectively appear to be the most abundant biological entities in the biosphere. With recent advances in metagenomics and metatranscriptomics, the known diversity of viruses substantially expanded. Comparative analysis of these viruses using advanced computational methods culminated in the reconstruction of the evolution of major groups of viruses and enabled the construction of a virus megataxonomy, which has been formally adopted by the International Committee on Taxonomy of Viruses. This comprehensive taxonomy consists of six virus realms, which are aspired to be monophyletic and assembled based on the conservation of hallmark proteins involved in capsid structure formation or genome replication. The viruses in different major taxa substantially differ in host range and accordingly in ecological niches. In this review article, we outline the latest developments in virus megataxonomy and the recent discoveries that will likely lead to reassessment of some major taxa, in particular, split of three of the current six realms into two or more independent realms. We then discuss the correspondence between virus taxonomy and the distribution of viruses among hosts and ecological niches, as well as the abundance of viruses versus cells in different habitats. The distribution of viruses across environments appears to be primarily determined by the host ranges, i.e. the virome is shaped by the composition of the biome in a given habitat, which itself is affected by abiotic factors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)
- Published
- 2024
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24. ICTV Virus Taxonomy Profile: Cruliviridae 2023.
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Kuhn JH, Adkins S, Brown K, de la Torre JC, Digiaro M, Hughes HR, Junglen S, Lambert AJ, Maes P, Marklewitz M, Palacios G, Sasaya T, Turina M, and Zhang YZ
- Subjects
- Negative-Sense RNA Viruses, Nucleoproteins, Open Reading Frames, RNA, RNA Viruses
- Abstract
Cruliviridae is a family of negative-sense RNA viruses with genomes of 10.8-11.5 kb that have been found in crustaceans. The crulivirid genome consists of three RNA segments with ORFs that encode a nucleoprotein (NP), a glycoprotein (GP), a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain, and in some family members, a zinc-finger (Z) protein of unknown function. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Cruliviridae , which is available at ictv.global/report/cruliviridae.
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- 2023
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25. ICTV Virus Taxonomy Profile: Tulasviridae 2023.
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Kuhn JH, Adkins S, Brown K, de la Torre JC, Digiaro M, Hughes HR, Junglen S, Lambert AJ, Maes P, Marklewitz M, Palacios G, Sasaya T, Zhang YZ, and Turina M
- Subjects
- Genome, Viral, Phylogeny, Nucleoproteins genetics, Virus Replication, Viruses genetics, RNA Viruses genetics
- Abstract
Tulasviridae is a family of ambisense RNA viruses with genomes of about 12.2 kb that have been found in fungi. The tulasvirid genome is nonsegmented and contains three open reading frames (ORFs) that encode a nucleoprotein (NP), a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain, and a protein of unknown function (X). This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Tulasviridae , which is available at ictv.global/report/tulasviridae.
- Published
- 2023
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26. ICTV Virus Taxonomy Profile: Mypoviridae 2023.
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Kuhn JH, Adkins S, Brown K, de la Torre JC, Digiaro M, Hughes HR, Junglen S, Lambert AJ, Maes P, Marklewitz M, Palacios G, Sasaya T, Turina M, and Zhang YZ
- Subjects
- Animals, Genome, Viral, Negative-Sense RNA Viruses, Virus Replication, Virion genetics, RNA Viruses genetics, Viruses genetics, Arthropods
- Abstract
Mypoviridae is a family of negative-sense RNA viruses with genomes of about 16.0 kb that have been found in myriapods. The mypovirid genome consists of three monocistronic RNA segments that encode a nucleoprotein (NP), a glycoprotein (GP), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Mypoviridae , which is available at: ictv.global/report/mypoviridae.
- Published
- 2023
- Full Text
- View/download PDF
27. ICTV Virus Taxonomy Profile: Leishbuviridae 2023.
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Adkins S, Brown K, de la Torre JC, Digiaro M, Hughes HR, Junglen S, Lambert AJ, Maes P, Marklewitz M, Palacios G, Sasaya 笹谷孝英 T, Turina M, Zhang 张永振 YZ, and Kuhn JH
- Subjects
- Negative-Sense RNA Viruses, Nucleoproteins genetics, Virus Replication, Virion genetics, Genome, Viral, RNA Viruses genetics
- Abstract
Leishbuviridae is a family of negative-sense RNA viruses with genomes of about 8.0 kb that have been found in protists. The leishbuvirid genome consists of three monocistronic RNA segments with open reading frames (ORFs) that encode a nucleoprotein (NP), a glycoprotein (GP), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Leishbuviridae , which is available at ictv.global/report/leishbuviridae.
- Published
- 2023
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28. ICTV Virus Taxonomy Profile: Wupedeviridae 2023.
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Kuhn JH, Adkins S, Brown K, de la Torre JC, Digiaro M, Hughes HR, Junglen S, Lambert AJ, Maes P, Marklewitz M, Palacios G, Sasaya T, Turina M, and Zhang YZ
- Subjects
- Animals, Genome, Viral, Negative-Sense RNA Viruses, Virus Replication, Virion genetics, RNA Viruses genetics, Viruses genetics, Arthropods
- Abstract
Wupedeviridae is a family of negative-sense RNA viruses with genomes of about 20.5 kb that have been found in myriapods. The wupedevirid genome consists of three monocistronic RNA segments with open reading frames (ORFs) that encode a nucleoprotein (NP), a glycoprotein (GP), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Wupedeviridae , which is available at ictv.global/report/wupedeviridae.
- Published
- 2023
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- View/download PDF
29. ICTV Virus Taxonomy Profile: Discoviridae 2023.
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Kuhn JH, Adkins S, Brown K, Carlos de la Torre J, Digiaro M, Hughes HR, Junglen S, Lambert AJ, Maes P, Marklewitz M, Palacios G, Sasaya T, Zhang YZ, and Turina M
- Subjects
- Genome, Viral, Negative-Sense RNA Viruses, Nucleoproteins genetics, Virus Replication, Virion genetics, RNA Viruses genetics, Viruses genetics
- Abstract
Discoviridae is a family of negative-sense RNA viruses with genomes of 6.2-9.7 kb that have been associated with fungi and stramenopiles. The discovirid genome consists of three monocistronic RNA segments with open reading frames (ORFs) that encode a nucleoprotein (NP), a nonstructural protein (Ns), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Discoviridae , which is available at ictv.global/report/discoviridae.
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- 2023
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- View/download PDF
30. ICTV Virus Taxonomy Profile: Jingchuvirales 2023.
- Author
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Kuhn JH, Dheilly NM, Junglen S, Paraskevopoulou S, Shi M, and Di Paola N
- Subjects
- Humans, Animals, Phylogeny, Nucleoproteins genetics, Negative-Sense RNA Viruses, Virus Replication, Virion, Genome, Viral, RNA Viruses genetics
- Abstract
Jingchuvirales is an order of negative-sense RNA viruses with genomes of 9.1-15.3 kb that have been associated with arachnids, barnacles, crustaceans, insects, fish and reptiles in Africa, Asia, Australia, Europe, North America and South America. The jingchuviral genome has two to four open reading frames (ORFs) that encode a glycoprotein (GP), a nucleoprotein (NP), a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain, and/or proteins of unknown function. Viruses in the order are only known from their genome sequences. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the order Jingchuvirales and on the families Aliusviridae , Chuviridae , Crepuscuviridae , Myriaviridae and Natareviridae , which are available at ictv.global/report/jingchuvirales, ictv.global/report/aliusviridae, ictv.global/report/chuviridae, ictv.global/report/crepuscuviridae, ictv.global/report/myriaviridae and ictv.global/report/natareviridae, respectively.
- Published
- 2023
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31. Novel machine-learning analysis of SARS-CoV-2 infection in a subclinical nonhuman primate model using radiomics and blood biomarkers.
- Author
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Chu WT, Castro MA, Reza S, Cooper TK, Bartlinski S, Bradley D, Anthony SM, Worwa G, Finch CL, Kuhn JH, Crozier I, and Solomon J
- Subjects
- Animals, SARS-CoV-2, Biomarkers, Machine Learning, Primates, COVID-19 diagnostic imaging
- Abstract
Detection of the physiological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is challenging in the absence of overt clinical signs but remains necessary to understand a full subclinical disease spectrum. In this study, our objective was to use radiomics (from computed tomography images) and blood biomarkers to predict SARS-CoV-2 infection in a nonhuman primate model (NHP) with inapparent clinical disease. To accomplish this aim, we built machine-learning models to predict SARS-CoV-2 infection in a NHP model of subclinical disease using baseline-normalized radiomic and blood sample analyses data from SARS-CoV-2-exposed and control (mock-exposed) crab-eating macaques. We applied a novel adaptation of the minimum redundancy maximum relevance (mRMR) feature-selection technique, called mRMR-permute, for statistically-thresholded and unbiased feature selection. Through performance comparison of eight machine-learning models trained on 14 feature sets, we demonstrated that a logistic regression model trained on the mRMR-permute feature set can predict SARS-CoV-2 infection with very high accuracy. Eighty-nine percent of mRMR-permute selected features had strong and significant class effects. Through this work, we identified a key set of radiomic and blood biomarkers that can be used to predict infection status even in the absence of clinical signs. Furthermore, we proposed and demonstrated the utility of a novel feature-selection technique called mRMR-permute. This work lays the foundation for the prediction and classification of SARS-CoV-2 disease severity., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Published
- 2023
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32. Repeatability of computed tomography liver radiomic features in a nonhuman primate model of diet-induced steatosis.
- Author
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Wang H, Solomon J, Reza SMS, Yang HJ, Chu WT, Crozier I, Sayre PJ, Lee BY, Mani V, Friedrich TC, O'Connor DH, Worwa G, Kuhn JH, Calcagno C, and Castro MA
- Abstract
Purpose: We describe a method to identify repeatable liver computed tomography (CT) radiomic features, suitable for detection of steatosis, in nonhuman primates. Criteria used for feature selection exclude nonrepeatable features and may be useful to improve the performance and robustness of radiomics-based predictive models., Approach: Six crab-eating macaques were equally assigned to two experimental groups, fed regular chow or an atherogenic diet. High-resolution CT images were acquired over several days for each macaque. First-order and second-order radiomic features were extracted from six regions in the liver parenchyma, either with or without liver-to-spleen intensity normalization from images reconstructed using either a standard (B-filter) or a bone-enhanced (D-filter) kernel. Intrasubject repeatability of each feature was assessed using a paired t -test for all scans and the minimum p -value was identified for each macaque. Repeatable features were defined as having a minimum p -value among all macaques above the significance level after Bonferroni's correction. Features showing a significant difference with respect to diet group were identified using a two-sample t -test., Results: A list of repeatable features was generated for each type of image. The largest number of repeatable features was achieved from spleen-normalized D-filtered images, which also produced the largest number of second-order radiomic features that were repeatable and different between diet groups., Conclusions: Repeatability depends on reconstruction kernel and normalization. Features were quantified and ranked based on their repeatability. Features to be excluded for more robust models were identified. Features that were repeatable but different between diet groups were also identified., (© 2023 Society of Photo-Optical Instrumentation Engineers (SPIE).)
- Published
- 2023
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33. Ectopic expression of murine CD163 enables cell-culture isolation of lactate dehydrogenase-elevating virus 63 years after its discovery.
- Author
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Shaw TM, Maloney SM, Nennig K, Ramuta MD, Norton A, Ibarra R, Kuehnert P, Brinton M, Faaberg K, Kuhn JH, O'Connor DH, Warren CJ, and Bailey AL
- Subjects
- Animals, Mice, Cell Line virology, Time Factors, Antigens, CD genetics, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic genetics, Antigens, Differentiation, Myelomonocytic metabolism, Cell Culture Techniques, Ectopic Gene Expression, Lactate dehydrogenase-elevating virus genetics, Lactate dehydrogenase-elevating virus growth & development, Lactate dehydrogenase-elevating virus immunology, Lactate dehydrogenase-elevating virus metabolism, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism
- Abstract
Importance: Mouse models of viral infection play an especially large role in virology. In 1960, a mouse virus, lactate dehydrogenase-elevating virus (LDV), was discovered and found to have the peculiar ability to evade clearance by the immune system, enabling it to persistently infect an individual mouse for its entire lifespan without causing overt disease. However, researchers were unable to grow LDV in culture, ultimately resulting in the demise of this system as a model of failed immunity. We solve this problem by identifying the cell-surface molecule CD163 as the critical missing component in cell-culture systems, enabling the growth of LDV in immortalized cell lines for the first time. This advance creates abundant opportunities for further characterizing LDV in order to study both failed immunity and the family of viruses to which LDV belongs, Arteriviridae (aka, arteriviruses)., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
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34. Correction to: Changes to virus taxonomy and the ICTV Statutes ratifed by the International Committee on Taxonomy of Viruses (2023).
- Author
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Zerbini FM, Siddell SG, Lefkowitz EJ, Mushegian AR, Adriaenssens EM, Alfenas-Zerbini P, Dempsey DM, Dutilh BE, García ML, Hendrickson RC, Junglen S, Krupovic M, Kuhn JH, Lambert AJ, Łobocka M, Oksanen HM, Robertson DL, Rubino L, Sabanadzovic S, Simmonds P, Smith DB, Suzuki N, Van Doorslaer K, Vandamme AM, and Varsani A
- Published
- 2023
- Full Text
- View/download PDF
35. ICTV Virus Taxonomy Profile: Yueviridae 2023.
- Author
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Krupovic M, Wolf YI, Koonin EV, and Kuhn JH
- Subjects
- Genome, Viral, Virion, RNA Viruses genetics
- Abstract
Yueviridae is a family of negative-sense RNA viruses with genomes of 7.8-8.2 kb that have been associated with crustaceans, insects, stramenopiles and plants. The yuevirid genome consist of two segments, each with at least one ORF. The large (L) segment ORF encodes a large protein containing an RNA-directed RNA polymerase domain. The small (S) segment ORF encodes a nucleocapsid protein. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Yueviridae , which is available at http://www.ictv.global/report/yueviridae.
- Published
- 2023
- Full Text
- View/download PDF
36. ICTV Virus Taxonomy Profile: Sunviridae 2023.
- Author
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Kuhn JH, Kurath G, Wolf YI, and Hyndman TH
- Subjects
- Phylogeny, Negative-Sense RNA Viruses, Virus Replication, Virion, Genome, Viral, RNA Viruses genetics
- Abstract
Sunviridae is a family of negative-sense RNA viruses with genomes of about 17.2 kb that have been found in snakes. The sunvirid genome comprises nonsegmented RNA with six open reading frames (ORFs) >1 kb that are predicted to encode six proteins. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Sunviridae , which is available at ictv.global/report/sunviridae.
- Published
- 2023
- Full Text
- View/download PDF
37. ICTV Virus Taxonomy Profile: Amnoonviridae 2023.
- Author
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Koonin EV, Krupovic M, Surachetpong W, Wolf YI, and Kuhn JH
- Subjects
- Animals, Phylogeny, Negative-Sense RNA Viruses, Open Reading Frames, Virus Replication, Genome, Viral, RNA Viruses genetics
- Abstract
Amnoonviridae is a family of negative-sense RNA viruses with genomes totalling about 10.3 kb. These viruses have been found in fish. The amnoonvirid genome consists of 10 segments, each with at least 1 open reading frame (ORF). The RNA1-3 ORFs encode the three subunits of the viral polymerase. The RNA4 ORF encodes a nucleoprotein. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Amnoonviridae , which is available at ictv.global/report/amnoonviridae.
- Published
- 2023
- Full Text
- View/download PDF
38. ICTV Virus Taxonomy Profile: Tosoviridae 2023.
- Author
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Wolf YI, Krupovic M, Kuhn JH, and Koonin EV
- Subjects
- Genome, Viral, RNA Viruses genetics
- Abstract
Tosoviridae is a family of negative-sense RNA viruses with genomes totaling about 12.3 kb that have been found in turtles. The tosovirid genome consists of two segments, each with two open reading frames (ORFs) in ambisense orientation. The small (S) segment encodes a nucleoprotein (NP) and a glycoprotein precursor (GPC); the large (L) segment encodes an L protein containing an RNA-directed RNA polymerase (RdRP) domain and a zinc-binding (Z) protein. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Tosoviridae , which is available at ictv.global/report/tosoviridae.
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- 2023
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39. ICTV Virus Taxonomy Profile: Qinviridae 2023.
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Wolf YI, Koonin EV, Krupovic M, and Kuhn JH
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- Animals, Insecta genetics, Crustacea, Phylogeny, Genome, Viral, Virus Replication, Virion genetics, RNA Viruses genetics
- Abstract
Qinviridae is a family of negative-sense RNA viruses with genomes of 7.3-8.2 kb that have been associated with crustaceans, insects, gastropods, and nematodes. The qinvirid genome consists of two segments, each with at least one open reading frame (ORF). The large (L) segment ORF encodes a large protein containing an RNA-directed RNA polymerase (RdRP) domain. The small (S) segment ORF encodes a nucleocapsid protein. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Qinviridae , which is available at ictv.global/report/qinviridae.
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- 2023
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40. Author Correction: Guidelines for public database submission of uncultivated virus genome sequences for taxonomic classification.
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Adriaenssens EM, Roux S, Brister JR, Karsch-Mizrachi I, Kuhn JH, Varsani A, Yigang T, Reyes A, Lood C, Lefkowitz EJ, Sullivan MB, Edwards RA, Simmonds P, Rubino L, Sabanadzovic S, Krupovic M, and Dutilh BE
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- 2023
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41. ICTV Virus Taxonomy Profile: Arenaviridae 2023.
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Radoshitzky SR, Buchmeier MJ, Charrel RN, Gonzalez JJ, Günther S, Hepojoki J, Kuhn JH, Lukashevich IS, Romanowski V, Salvato MS, Sironi M, Stenglein MD, and Torre JC
- Subjects
- Animals, Nucleoproteins genetics, RNA, RNA-Dependent RNA Polymerase, Mammals, Arenaviridae genetics
- Abstract
Arenaviridae is a family for ambisense RNA viruses with genomes of about 10.5 kb that infect mammals, snakes, and fish. The arenavirid genome consists of two or three single-stranded RNA segments and encodes a nucleoprotein (NP), a glycoprotein (GP) and a large (L) protein containing RNA-directed RNA polymerase (RdRP) domains; some arenavirids encode a zinc-binding protein (Z). This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Arenaviridae , which is available at www.ictv.global/report/arenaviridae.
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- 2023
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42. Deep-Learning-Based Whole-Lung and Lung-Lesion Quantification Despite Inconsistent Ground Truth: Application to Computerized Tomography in SARS-CoV-2 Nonhuman Primate Models.
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Reza SMS, Chu WT, Homayounieh F, Blain M, Firouzabadi FD, Anari PY, Lee JH, Worwa G, Finch CL, Kuhn JH, Malayeri A, Crozier I, Wood BJ, Feuerstein IM, and Solomon J
- Subjects
- Animals, Lung diagnostic imaging, Primates, SARS-CoV-2, Tomography, X-Ray Computed methods, COVID-19 diagnostic imaging, Deep Learning
- Abstract
Rationale and Objectives: Animal modeling of infectious diseases such as coronavirus disease 2019 (COVID-19) is important for exploration of natural history, understanding of pathogenesis, and evaluation of countermeasures. Preclinical studies enable rigorous control of experimental conditions as well as pre-exposure baseline and longitudinal measurements, including medical imaging, that are often unavailable in the clinical research setting. Computerized tomography (CT) imaging provides important diagnostic, prognostic, and disease characterization to clinicians and clinical researchers. In that context, automated deep-learning systems for the analysis of CT imaging have been broadly proposed, but their practical utility has been limited. Manual outlining of the ground truth (i.e., lung-lesions) requires accurate distinctions between abnormal and normal tissues that often have vague boundaries and is subject to reader heterogeneity in interpretation. Indeed, this subjectivity is demonstrated as wide inconsistency in manual outlines among experts and from the same expert. The application of deep-learning data-science tools has been less well-evaluated in the preclinical setting, including in nonhuman primate (NHP) models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/COVID-19, in which the translation of human-derived deep-learning tools is challenging. The automated segmentation of the whole lung and lung lesions provides a potentially standardized and automated method to detect and quantify disease., Materials and Methods: We used deep-learning-based quantification of the whole lung and lung lesions on CT scans of NHPs exposed to SARS-CoV-2. We proposed a novel multi-model ensemble technique to address the inconsistency in the ground truths for deep-learning-based automated segmentation of the whole lung and lung lesions. Multiple models were obtained by training the convolutional neural network (CNN) on different subsets of the training data instead of having a single model using the entire training dataset. Moreover, we employed a feature pyramid network (FPN), a CNN that provides predictions at different resolution levels, enabling the network to predict objects with wide size variations., Results: We achieved an average of 99.4 and 60.2% Dice coefficients for whole-lung and lung-lesion segmentation, respectively. The proposed multi-model FPN outperformed well-accepted methods U-Net (50.5%), V-Net (54.5%), and Inception (53.4%) for the challenging lesion-segmentation task. We show the application of segmentation outputs for longitudinal quantification of lung disease in SARS-CoV-2-exposed and mock-exposed NHPs., Conclusion: Deep-learning methods should be optimally characterized for and targeted specifically to preclinical research needs in terms of impact, automation, and dynamic quantification independently from purely clinical applications., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Inc.)
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- 2023
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43. Renaming of the genus Flavivirus to Orthoflavivirus and extension of binomial species names within the family Flaviviridae.
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Postler TS, Beer M, Blitvich BJ, Bukh J, de Lamballerie X, Drexler JF, Imrie A, Kapoor A, Karganova GG, Lemey P, Lohmann V, Simmonds P, Smith DB, Stapleton JT, and Kuhn JH
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- Hepacivirus, Terminology as Topic, Flaviviridae genetics, Flavivirus genetics
- Abstract
This review provides a summary of the recently ratified changes to genus and species nomenclature within the virus family Flaviviridae along with reasons for these changes. First, it was considered that the vernacular terms "flaviviral", "flavivirus", and "flaviviruses" could under certain circumstances be ambiguous due to the same word stem "flavi" in the taxon names Flaviviridae and Flavivirus; these terms could either have referred to all viruses classified in the family Flaviviridae or only to viruses classified in the included genus Flavivirus. To remove this ambiguity, the genus name Flavivirus was changed to Orthoflavivirus by the International Committee on Taxonomy of Viruses (ICTV). Second, all species names in the family were changed to adhere to a newly ICTV-mandated binomial format (e.g., Orthoflavivirus zikaense, Hepacivirus hominis) similar to nomenclature conventions used for species elsewhere in biology. It is important to note, however, that virus names remain unchanged. Here we outline the revised taxonomy of the family Flaviviridae as approved by the ICTV in April 2023., (© 2023. Springer-Verlag GmbH Austria, part of Springer Nature.)
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- 2023
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44. Efficacy of microbicidal actives and formulations for inactivation of Lassa virus in suspension.
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Cutts TA, Nims RW, Rubino JR, McKinney J, Kuhn JH, and Ijaz MK
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- Animals, Chlorocebus aethiops, Humans, Lassa virus, Vero Cells, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Lassa Fever prevention & control, Anti-Infective Agents metabolism, Disinfectants pharmacology, Disinfectants metabolism
- Abstract
The World Health Organization's R&D Blueprint list of priority diseases for 2022 includes Lassa fever, signifying the need for research and development in emergency contexts. This disease is caused by the arenavirus Lassa virus (LASV). Being an enveloped virus, LASV should be susceptible to a variety of microbicidal actives, although empirical data to support this expectation are needed. We evaluated the virucidal efficacy of sodium hypochlorite, ethanol, a formulated dual quaternary ammonium compound, an accelerated hydrogen peroxide formulation, and a p-chloro-m-xylenol formulation, per ASTM E1052-20, against LASV engineered to express green fluorescent protein (GFP). A 10-μL volume of virus in tripartite soil (bovine serum albumin, tryptone, and mucin) was combined with 50 μL of disinfectant in suspension for 0.5, 1, 5, or 10 min at 20-25 °C. Neutralized test mixtures were quantified by GFP expression to determine log
10 reduction. Remaining material was passaged on Vero cells to confirm absence of residual infectious virus. Input virus titers of 6.6-8.0 log10 per assay were completely inactivated by each disinfectant within 1-5 min contact time. The rapid and substantial inactivation of LASV suggests the utility of these microbicides for mitigating spread of infectious virus during Lassa fever outbreaks., (© 2023. Springer Nature Limited.)- Published
- 2023
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45. Renaming of genera Ebolavirus and Marburgvirus to Orthoebolavirus and Orthomarburgvirus, respectively, and introduction of binomial species names within family Filoviridae.
- Author
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Biedenkopf N, Bukreyev A, Chandran K, Di Paola N, Formenty PBH, Griffiths A, Hume AJ, Mühlberger E, Netesov SV, Palacios G, Pawęska JT, Smither S, Takada A, Wahl V, and Kuhn JH
- Subjects
- Marburgvirus, Ebolavirus, Filoviridae, Viruses
- Abstract
The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group continues to prospectively refine the established nomenclature for taxa included in family Filoviridae in an effort to decrease confusion of genus, species, and virus names and to adhere to amended stipulations of the International Code of Virus Classification and Nomenclature (ICVCN). Recently, the genus names Ebolavirus and Marburgvirus were changed to Orthoebolavirus and Orthomarburgvirus, respectively. Additionally, all established species names in family Filoviridae now adhere to the ICTV-mandated binomial format. Virus names remain unchanged and valid. Here, we outline the revised taxonomy of family Filoviridae as approved by the ICTV in April 2023., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2023
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46. Annual (2023) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria : kingdom Orthornavirae : phylum Negarnaviricota ).
- Author
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Kuhn JH, Abe J, Adkins S, Alkhovsky SV, Avšič-Županc T, Ayllón MA, Bahl J, Balkema-Buschmann A, Ballinger MJ, Kumar Baranwal V, Beer M, Bejerman N, Bergeron É, Biedenkopf N, Blair CD, Blasdell KR, Blouin AG, Bradfute SB, Briese T, Brown PA, Buchholz UJ, Buchmeier MJ, Bukreyev A, Burt F, Büttner C, Calisher CH, Cao M, Casas I, Chandran K, Charrel RN, Kumar Chaturvedi K, Chooi KM, Crane A, Dal Bó E, Carlos de la Torre J, de Souza WM, de Swart RL, Debat H, Dheilly NM, Di Paola N, Di Serio F, Dietzgen RG, Digiaro M, Drexler JF, Duprex WP, Dürrwald R, Easton AJ, Elbeaino T, Ergünay K, Feng G, Firth AE, Fooks AR, Formenty PBH, Freitas-Astúa J, Gago-Zachert S, Laura García M, García-Sastre A, Garrison AR, Gaskin TR, Gong W, Gonzalez JJ, de Bellocq J, Griffiths A, Groschup MH, Günther I, Günther S, Hammond J, Hasegawa Y, Hayashi K, Hepojoki J, Higgins CM, Hongō S, Horie M, Hughes HR, Hume AJ, Hyndman TH, Ikeda K, Jiāng D, Jonson GB, Junglen S, Klempa B, Klingström J, Kondō H, Koonin EV, Krupovic M, Kubota K, Kurath G, Laenen L, Lambert AJ, Lǐ J, Li JM, Liu R, Lukashevich IS, MacDiarmid RM, Maes P, Marklewitz M, Marshall SH, Marzano SL, McCauley JW, Mirazimi A, Mühlberger E, Nabeshima T, Naidu R, Natsuaki T, Navarro B, Navarro JA, Neriya Y, Netesov SV, Neumann G, Nowotny N, Nunes MRT, Ochoa-Corona FM, Okada T, Palacios G, Pallás V, Papa A, Paraskevopoulou S, Parrish CR, Pauvolid-Corrêa A, Pawęska JT, Pérez DR, Pfaff F, Plemper RK, Postler TS, Rabbidge LO, Radoshitzky SR, Ramos-González PL, Rehanek M, Resende RO, Reyes CA, Rodrigues TCS, Romanowski V, Rubbenstroth D, Rubino L, Runstadler JA, Sabanadzovic S, Sadiq S, Salvato MS, Sasaya T, Schwemmle M, Sharpe SR, Shi M, Shimomoto Y, Kavi Sidharthan V, Sironi M, Smither S, Song JW, Spann KM, Spengler JR, Stenglein MD, Takada A, Takeyama S, Tatara A, Tesh RB, Thornburg NJ, Tian X, Tischler ND, Tomitaka Y, Tomonaga K, Tordo N, Tu C, Turina M, Tzanetakis IE, Maria Vaira A, van den Hoogen B, Vanmechelen B, Vasilakis N, Verbeek M, von Bargen S, Wada J, Wahl V, Walker PJ, Waltzek TB, Whitfield AE, Wolf YI, Xia H, Xylogianni E, Yanagisawa H, Yano K, Ye G, Yuan Z, Zerbini FM, Zhang G, Zhang S, Zhang YZ, Zhao L, and Økland AL
- Subjects
- RNA-Dependent RNA Polymerase genetics, Negative-Sense RNA Viruses, RNA Viruses genetics
- 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.
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- 2023
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47. Guidelines for public database submission of uncultivated virus genome sequences for taxonomic classification.
- Author
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Adriaenssens EM, Roux S, Brister JR, Karsch-Mizrachi I, Kuhn JH, Varsani A, Yigang T, Reyes A, Lood C, Lefkowitz EJ, Sullivan MB, Edwards RA, Simmonds P, Rubino L, Sabanadzovic S, Krupovic M, and Dutilh BE
- Subjects
- Phylogeny, Databases, Factual, Genome, Viral genetics
- Published
- 2023
- Full Text
- View/download PDF
48. Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission.
- Author
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Bellomo CM, Alonso DO, Pérez-Sautu U, Prieto K, Kehl S, Coelho RM, Periolo N, Di Paola N, Ferressini-Gerpe N, Kuhn JH, Sanchez-Lockhart M, Palacios G, and Martínez VP
- Subjects
- Cricetinae, Animals, Humans, Mesocricetus, Models, Animal, Genome, Viral, Orthohantavirus genetics, Hantavirus Pulmonary Syndrome genetics
- Abstract
We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks., Competing Interests: The authors declare no conflict of interest.
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- 2023
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49. Computed Tomography Imaging for Monitoring of Marburg Virus Disease: a Nonhuman Primate Proof-Of-Concept Study.
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Sword J, Lee JH, Castro MA, Solomon J, Aiosa N, Reza SMS, Chu WT, Johnson JC, Bartos C, Cooper K, Jahrling PB, Johnson RF, Calcagno C, Crozier I, Kuhn JH, Hensley LE, Feuerstein IM, and Mani V
- Subjects
- Humans, Animals, Pilot Projects, Tomography, X-Ray Computed, Disease Progression, Primates, Marburg Virus Disease diagnostic imaging, Marburg Virus Disease pathology, Marburgvirus
- Abstract
Marburg virus (MARV) is a highly virulent zoonotic filovirid that causes Marburg virus disease (MVD) in humans. The pathogenesis of MVD remains poorly understood, partially due to the low number of cases that can be studied, the absence of state-of-the-art medical equipment in areas where cases are reported, and limitations on the number of animals that can be safely used in experimental studies under maximum containment animal biosafety level 4 conditions. Medical imaging modalities, such as whole-body computed tomography (CT), may help to describe disease progression in vivo , potentially replacing ethically contentious and logistically challenging serial euthanasia studies. Towards this vision, we performed a pilot study, during which we acquired whole-body CT images of 6 rhesus monkeys before and 7 to 9 days after intramuscular MARV exposure. We identified imaging abnormalities in the liver, spleen, and axillary lymph nodes that corresponded to clinical, virological, and gross pathological hallmarks of MVD in this animal model. Quantitative image analysis indicated hepatomegaly with a significant reduction in organ density (indicating fatty infiltration of the liver), splenomegaly, and edema that corresponded with gross pathological and histopathological findings. Our results indicated that CT imaging could be used to verify and quantify typical MVD pathogenesis versus altered, diminished, or absent disease severity or progression in the presence of candidate medical countermeasures, thus possibly reducing the number of animals needed and eliminating serial euthanasia. IMPORTANCE Marburg virus (MARV) is a highly virulent zoonotic filovirid that causes Marburg virus disease (MVD) in humans. Much is unknown about disease progression and, thus, prevention and treatment options are limited. Medical imaging modalities, such as whole-body computed tomography (CT), have the potential to improve understanding of MVD pathogenesis. Our study used CT to identify abnormalities in the liver, spleen, and axillary lymph nodes that corresponded to known clinical signs of MVD in this animal model. Our results indicated that CT imaging and analyses could be used to elucidate pathogenesis and possibly assess the efficacy of candidate treatments., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
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50. Magnetic Resonance Imaging for Monitoring of Hepatic Disease Induced by Ebola Virus: a Nonhuman Primate Proof-of-Concept Study.
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Lee JH, Calcagno C, Feuerstein IM, Solomon J, Mani V, Huzella L, Castro MA, Laux J, Reeder RJ, Kim DY, Worwa G, Thomasson D, Hagen KR, Ragland DR, Kuhn JH, and Johnson RF
- Subjects
- Animals, Macaca mulatta, Magnetic Resonance Imaging, Disease Models, Animal, Ebolavirus, Hemorrhagic Fever, Ebola, Liver Diseases
- Abstract
Severe liver impairment is a well-known hallmark of Ebola virus disease (EVD). However, the role of hepatic involvement in EVD progression is understudied. Medical imaging in established animal models of EVD (e.g., nonhuman primates [NHPs]) can be a strong complement to traditional assays to better investigate this pathophysiological process in vivo and noninvasively. In this proof-of-concept study, we used longitudinal multiparametric magnetic resonance imaging (MRI) to characterize liver morphology and function in nine rhesus monkeys after exposure to Ebola virus (EBOV). Starting 5 days postexposure, MRI assessments of liver appearance, morphology, and size were consistently compatible with the presence of hepatic edema, inflammation, and congestion, leading to significant hepatomegaly at necropsy. MRI performed after injection of a hepatobiliary contrast agent demonstrated decreased liver signal on the day of euthanasia, suggesting progressive hepatocellular dysfunction and hepatic secretory impairment associated with EBOV infection. Importantly, MRI-assessed deterioration of biliary function was acute and progressed faster than changes in serum bilirubin concentrations. These findings suggest that longitudinal quantitative in vivo imaging may be a useful addition to standard biological assays to gain additional knowledge about organ pathophysiology in animal models of EVD. IMPORTANCE Severe liver impairment is a well-known hallmark of Ebola virus disease (EVD), but the contribution of hepatic pathophysiology to EVD progression is not fully understood. Noninvasive medical imaging of liver structure and function in well-established animal models of disease may shed light on this important aspect of EVD. In this proof-of-concept study, we used longitudinal magnetic resonance imaging (MRI) to characterize liver abnormalities and dysfunction in rhesus monkeys exposed to Ebola virus. The results indicate that in vivo MRI may be used as a noninvasive readout of organ pathophysiology in EVD and may be used in future animal studies to further characterize organ-specific damage of this condition, in addition to standard biological assays., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
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- View/download PDF
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