{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T01:31:22Z","timestamp":1780968682038,"version":"3.54.1"},"reference-count":157,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center of Excellence of Influenza Research and Surveillance (CEIRS)","award":["HHSN272201400004C"],"award-info":[{"award-number":["HHSN272201400004C"]}]},{"name":"Center of Excellence of Influenza Research and Surveillance (CEIRS)","award":["75N93021C00018"],"award-info":[{"award-number":["75N93021C00018"]}]},{"name":"NIAID Centers of Excellence for Influenza Research and Response, CEIRR","award":["HHSN272201400004C"],"award-info":[{"award-number":["HHSN272201400004C"]}]},{"name":"NIAID Centers of Excellence for Influenza Research and Response, CEIRR","award":["75N93021C00018"],"award-info":[{"award-number":["75N93021C00018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza A (IAV) is a major human respiratory pathogen that causes illness, hospitalizations, and mortality annually worldwide. IAV is also a zoonotic pathogen with a multitude of hosts, allowing for interspecies transmission, reassortment events, and the emergence of novel pandemics, as was seen in 2009 with the emergence of a swine-origin H1N1 (pdmH1N1) virus into humans, causing the first influenza pandemic of the 21st century. While the 2009 pandemic was considered to have high morbidity and low mortality, studies have linked the pdmH1N1 virus and its gene segments to increased disease in humans and animal models. Genetic components of the pdmH1N1 virus currently circulate in the swine population, reassorting with endemic swine viruses that co-circulate and occasionally spillover into humans. This is evidenced by the regular detection of variant swine IAVs in humans associated with state fairs and other intersections of humans and swine. Defining genetic changes that support species adaptation, virulence, and cross-species transmission, as well as mutations that enhance or attenuate these features, will improve our understanding of influenza biology. It aids in surveillance and virus risk assessment and guides the establishment of counter measures for emerging viruses. Here, we review the current understanding of the determinants of specific IAV phenotypes, focusing on the fitness, transmission, and virulence determinants that have been identified in swine IAVs and\/or in relation to the 2009 pdmH1N1 virus.<\/jats:p>","DOI":"10.3390\/v15091959","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T21:47:03Z","timestamp":1695246423000},"page":"1959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Fitness Determinants of Influenza A Viruses"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5616-8118","authenticated-orcid":false,"given":"Emily Fate","family":"Griffin","sequence":"first","affiliation":[{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"},{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"},{"name":"Emory-UGA Centers of Excellence for Influenza Research and Surveillance (CEIRS), Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-5588","authenticated-orcid":false,"given":"Stephen Mark","family":"Tompkins","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"},{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"},{"name":"Emory-UGA Centers of Excellence for Influenza Research and Surveillance (CEIRS), Athens, GA 30602, USA"},{"name":"Center for Influenza Disease and Emergence Response (CIDER), Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"ref_1","first-page":"43","article-title":"Seasonal influenza vaccines","volume":"333","author":"Fiore","year":"2009","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_2","unstructured":"Knipe, D.M., and Howley, P.M. (2013). Fields Virology, Wolters Kluwer\/Lippincott Williams & Wilkins Health. [6th ed.]."},{"key":"ref_3","unstructured":"World Health Organization (2019, October 31). Influenza (Seasonal) Fact Sheet N211. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/influenza-(seasonal)."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1126\/science.1176225","article-title":"Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans","volume":"325","author":"Garten","year":"2009","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1751-0813.2011.00844.x","article-title":"The first identified case of pandemic H1N1 influenza in pigs in Australia","volume":"89","author":"Holyoake","year":"2011","journal-title":"Aust. Vet. J."},{"key":"ref_6","first-page":"1153","article-title":"An investigation into human pandemic influenza virus (H1N1) 2009 on an Alberta swine farm","volume":"50","author":"Howden","year":"2009","journal-title":"Can. Vet. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3201\/eid1602.091230","article-title":"Pandemic (H1N1) 2009 outbreak on pig farm, Argentina","volume":"16","author":"Pereda","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/irv.12075","article-title":"Virus-specific factors associated with zoonotic and pandemic potential","volume":"7","author":"Capua","year":"2013","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1128\/mr.56.1.152-179.1992","article-title":"Evolution and ecology of influenza A viruses","volume":"56","author":"Webster","year":"1992","journal-title":"Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.virol.2005.02.003","article-title":"Receptor specificity of influenza viruses from birds and mammals: New data on involvement of the inner fragments of the carbohydrate chain","volume":"334","author":"Gambaryan","year":"2005","journal-title":"Virology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8502","DOI":"10.1128\/JVI.74.18.8502-8512.2000","article-title":"Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals","volume":"74","author":"Matrosovich","year":"2000","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0042-6822(83)90150-2","article-title":"Receptor determinants of human and animal influenza virus isolates: Differences in receptor specificity of the H3 hemagglutinin based on species of origin","volume":"127","author":"Rogers","year":"1983","journal-title":"Virology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1016\/j.vaccine.2012.04.049","article-title":"Adaptive pathways of zoonotic influenza viruses: From exposure to establishment in humans","volume":"30","author":"Reperant","year":"2012","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.cell.2013.05.035","article-title":"Structural determinants for naturally evolving H5N1 hemagglutinin to switch its receptor specificity","volume":"153","author":"Tharakaraman","year":"2013","journal-title":"Cell"},{"key":"ref_15","unstructured":"Zimmerman, J.J., Straw, B.E., D\u2019Allaire, S., and Taylor, D.J. (2006). Diseases of Swine, Blackwell Pub.. [9th ed.]."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1084\/jem.54.3.373","article-title":"Swine Influenza: III. Filtration Experiments and Etiology","volume":"54","author":"Shope","year":"1931","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0168-1702(02)00027-8","article-title":"The emergence of novel swine influenza viruses in North America","volume":"85","author":"Olsen","year":"2002","journal-title":"Virus Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8851","DOI":"10.1128\/JVI.73.10.8851-8856.1999","article-title":"Genetic reassortment of avian, swine, and human influenza A viruses in American pigs","volume":"73","author":"Zhou","year":"1999","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0065-3527(08)00403-X","article-title":"Swine influenza viruses a North American perspective","volume":"72","author":"Vincent","year":"2008","journal-title":"Adv. Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1750-2659.2010.00189.x","article-title":"Genetic composition of contemporary swine influenza viruses in the West Central region of the United States of America","volume":"5","author":"Evseenko","year":"2011","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1099\/vir.0.027557-0","article-title":"Genetic and antigenic characterization of H1 influenza viruses from United States swine from 2008","volume":"92","author":"Lorusso","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/j.1865-1682.2011.01219.x","article-title":"Molecular and antigenic characterization of triple-reassortant H3N2 swine influenza viruses isolated from pigs, turkey and quail in Canada","volume":"58","author":"Nfon","year":"2011","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8667","DOI":"10.1128\/JVI.00801-11","article-title":"Characterization of H1N1 swine influenza viruses circulating in Canadian pigs in 2009","volume":"85","author":"Nfon","year":"2011","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e16777","DOI":"10.7554\/eLife.16777","article-title":"Origins of the 2009 H1N1 influenza pandemic in swine in Mexico","volume":"5","author":"Mena","year":"2016","journal-title":"eLife"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team (2009). Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N. Engl. J. Med., 360, 2605\u20132615.","DOI":"10.1056\/NEJMoa0903810"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nature08182","article-title":"Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic","volume":"459","author":"Smith","year":"2009","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/irv.12074","article-title":"Estimating age-specific cumulative incidence for the 2009 influenza pandemic: A meta-analysis of A(H1N1)pdm09 serological studies from 19 countries","volume":"7","author":"Hirve","year":"2013","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.3201\/1709.110338","article-title":"Multiple reassortment between pandemic (H1N1) 2009 and endemic influenza viruses in pigs, United States","volume":"17","author":"Ducatez","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19406","DOI":"10.2807\/ese.14.45.19406-en","article-title":"Pandemic influenza A(H1N1)v: Human to pig transmission in Norway?","volume":"14","author":"Hofshagen","year":"2009","journal-title":"Eurosurveillance"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11262-011-0597-5","article-title":"Brief report: Molecular characterization of a novel reassorted pandemic H1N1 2009 in Thai pigs","volume":"43","author":"Kitikoon","year":"2011","journal-title":"Virus Genes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/zph.12235","article-title":"Serological Evidence of Pandemic H1N1 Influenza Virus Infections in Greek Swine","volume":"63","author":"Kyriakis","year":"2016","journal-title":"Zoonoses Public Health"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6218","DOI":"10.1128\/JVI.00459-15","article-title":"Continual Reintroduction of Human Pandemic H1N1 Influenza A Viruses into Swine in the United States, 2009 to 2014","volume":"89","author":"Nelson","year":"2015","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.tim.2014.12.002","article-title":"Reverse zoonosis of influenza to swine: New perspectives on the human-animal interface","volume":"23","author":"Nelson","year":"2015","journal-title":"Trends Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Simon, G., Larsen, L.E., Durrwald, R., Foni, E., Harder, T., Van Reeth, K., Markowska-Daniel, I., Reid, S.M., Dan, A., and Maldonado, J. (2014). European surveillance network for influenza in pigs: Surveillance programs, diagnostic tools and Swine influenza virus subtypes identified in 14 European countries from 2010 to 2013. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115815"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e01763-16","DOI":"10.1128\/JVI.01763-16","article-title":"Reassortment between Swine H3N2 and 2009 Pandemic H1N1 in the United States Resulted in Influenza A Viruses with Diverse Genetic Constellations with Variable Virulence in Pigs","volume":"91","author":"Rajao","year":"2017","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/irv.12559","article-title":"Regional patterns of genetic diversity in swine influenza A viruses in the United States from 2010 to 2016","volume":"13","author":"Walia","year":"2019","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e3915","DOI":"10.7717\/peerj.3915","article-title":"Pulmonary transcriptomic responses indicate a dual role of inflammation in pneumonia development and viral clearance during 2009 pandemic influenza infection","volume":"5","author":"Almansa","year":"2017","journal-title":"PeerJ"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/nature08260","article-title":"In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses","volume":"460","author":"Itoh","year":"2009","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mishra, A.C., Chadha, M.S., Choudhary, M.L., and Potdar, V.A. (2010). Pandemic influenza (H1N1) 2009 is associated with severe disease in India. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010540"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1128\/JVI.01848-10","article-title":"Pandemic swine-origin H1N1 influenza A virus isolates show heterogeneous virulence in macaques","volume":"85","author":"Safronetz","year":"2011","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.3201\/eid2309.170847","article-title":"Influenza A(H3N2) Virus in Swine at Agricultural Fairs and Transmission to Humans, Michigan and Ohio, USA, 2016","volume":"23","author":"Bowman","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10963","DOI":"10.1128\/JVI.01457-16","article-title":"Introduction, Evolution, and Dissemination of Influenza A Viruses in Exhibition Swine in the United States during 2009 to 2013","volume":"90","author":"Nelson","year":"2016","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lloren, K.K.S., Lee, T., Kwon, J.J., and Song, M.S. (2017). Molecular Markers for Interspecies Transmission of Avian Influenza Viruses in Mammalian Hosts. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122706"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lin, R.W., Chen, G.W., Sung, H.H., Lin, R.J., Yen, L.C., Tseng, Y.L., Chang, Y.K., Lien, S.P., Shih, S.R., and Liao, C.L. (2019). Naturally occurring mutations in PB1 affect influenza A virus replication fidelity, virulence, and adaptability. J. Biomed. Sci., 26.","DOI":"10.1186\/s12929-019-0547-4"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1128\/JVI.02634-09","article-title":"Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission","volume":"84","author":"Herfst","year":"2010","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2010.02.024","article-title":"Substitution of lysine at 627 position in PB2 protein does not change virulence of the 2009 pandemic H1N1 virus in mice","volume":"401","author":"Zhu","year":"2010","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1128\/JVI.05699-11","article-title":"Combination of PB2 271A and SR polymorphism at positions 590\/591 is critical for viral replication and virulence of swine influenza virus in cultured cells and in vivo","volume":"86","author":"Liu","year":"2012","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yamada, S., Hatta, M., Staker, B.L., Watanabe, S., Imai, M., Shinya, K., Sakai-Tagawa, Y., Ito, M., Ozawa, M., and Watanabe, T. (2010). Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001034"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lam, T.T., Hon, C.C., Pybus, O.G., Kosakovsky Pond, S.L., Wong, R.T., Yip, C.W., Zeng, F., and Leung, F.C. (2008). Evolutionary and transmission dynamics of reassortant H5N1 influenza virus in Indonesia. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000130"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8042","DOI":"10.1128\/JVI.00901-15","article-title":"Identification of Influenza A Virus PB2 Residues Involved in Enhanced Polymerase Activity and Virus Growth in Mammalian Cells at Low Temperatures","volume":"89","author":"Hayashi","year":"2015","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1128\/JVI.03024-13","article-title":"PB2-588I enhances 2009 H1N1 pandemic influenza virus virulence by increasing viral replication and exacerbating PB2 inhibition of beta interferon expression","volume":"88","author":"Zhao","year":"2014","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1128\/jvi.67.4.1761-1764.1993","article-title":"A single amino acid in the PB2 gene of influenza A virus is a determinant of host range","volume":"67","author":"Subbarao","year":"1993","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1126\/science.1115273","article-title":"Highly pathogenic H5N1 influenza virus infection in migratory birds","volume":"309","author":"Liu","year":"2005","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.virol.2003.11.030","article-title":"PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice","volume":"320","author":"Shinya","year":"2004","journal-title":"Virology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.rvsc.2017.11.006","article-title":"The PB2-K627E mutation attenuates H3N2 swine influenza virus in cultured cells and in mice","volume":"117","author":"Gong","year":"2018","journal-title":"Res. Vet. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1126\/science.1213362","article-title":"Airborne transmission of influenza A\/H5N1 virus between ferrets","volume":"336","author":"Herfst","year":"2012","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5398","DOI":"10.1128\/JVI.75.11.5398-5404.2001","article-title":"Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses","volume":"75","author":"Massin","year":"2001","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.chom.2008.06.007","article-title":"An inhibitory activity in human cells restricts the function of an avian-like influenza virus polymerase","volume":"4","author":"Mehle","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1128\/JVI.00977-08","article-title":"Avian Influenza A virus polymerase association with nucleoprotein, but not polymerase assembly, is impaired in human cells during the course of infection","volume":"83","author":"Tomoiu","year":"2009","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature16474","article-title":"Species difference in ANP32A underlies influenza A virus polymerase host restriction","volume":"529","author":"Long","year":"2016","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4395","DOI":"10.1128\/JVI.02642-09","article-title":"PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells","volume":"84","author":"Bussey","year":"2010","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12058","DOI":"10.1128\/JVI.79.18.12058-12064.2005","article-title":"Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model","volume":"79","author":"Li","year":"2005","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Steel, J., Lowen, A.C., Mubareka, S., and Palese, P. (2009). Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E\/701N. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000252"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Gabriel, G., Herwig, A., and Klenk, H.D. (2008). Interaction of polymerase subunit PB2 and NP with importin alpha1 is a determinant of host range of influenza A virus. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.0040011"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1038\/ncomms6509","article-title":"The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication","volume":"5","author":"Song","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1128\/JVI.01694-10","article-title":"PB2 residue 158 is a pathogenic determinant of pandemic H1N1 and H5 influenza a viruses in mice","volume":"85","author":"Zhou","year":"2011","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13432","DOI":"10.1128\/JVI.05266-11","article-title":"Indications that live poultry markets are a major source of human H5N1 influenza virus infection in China","volume":"85","author":"Wan","year":"2011","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5021","DOI":"10.1038\/ncomms6021","article-title":"Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts","volume":"5","author":"Fan","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1128\/JVI.02387-15","article-title":"Glycine at Position 622 in PB1 Contributes to the Virulence of H5N1 Avian Influenza Virus in Mice","volume":"90","author":"Feng","year":"2016","journal-title":"J. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4603","DOI":"10.1128\/jvi.63.11.4603-4608.1989","article-title":"Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics","volume":"63","author":"Kawaoka","year":"1989","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.3201\/eid1512.090845","article-title":"Genomic signatures of influenza A pandemic (H1N1) 2009 virus","volume":"15","author":"Chen","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1099\/vir.0.036434-0","article-title":"Amino acids 473V and 598P of PB1 from an avian-origin influenza A virus contribute to polymerase activity, especially in mammalian cells","volume":"93","author":"Xu","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1128\/JVI.02717-09","article-title":"PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models","volume":"84","author":"Hai","year":"2010","journal-title":"J. Virol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Chen, L.M., Davis, C.T., Zhou, H., Cox, N.J., and Donis, R.O. (2008). Genetic compatibility and virulence of reassortants derived from contemporary avian H5N1 and human H3N2 influenza A viruses. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000072"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1348-0421.2002.tb02682.x","article-title":"Fine mapping of the subunit binding sites of influenza virus RNA polymerase","volume":"46","author":"Ohtsu","year":"2002","journal-title":"Microbiol. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"18590","DOI":"10.1073\/pnas.0507415102","article-title":"The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host","volume":"102","author":"Gabriel","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kamiki, H., Matsugo, H., Kobayashi, T., Ishida, H., Takenaka-Uema, A., Murakami, S., and Horimoto, T. (2018). A PB1-K577E Mutation in H9N2 Influenza Virus Increases Polymerase Activity and Pathogenicity in Mice. Viruses, 10.","DOI":"10.3390\/v10110653"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"10807","DOI":"10.1128\/JVI.74.22.10807-10810.2000","article-title":"Molecular correlates of influenza A H5N1 virus pathogenesis in mice","volume":"74","author":"Katz","year":"2000","journal-title":"J. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/nature04230","article-title":"Characterization of the 1918 influenza virus polymerase genes","volume":"437","author":"Taubenberger","year":"2005","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1128\/JVI.01565-12","article-title":"Virulence determinants of pandemic A(H1N1)2009 influenza virus in a mouse model","volume":"87","author":"Uraki","year":"2013","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"11981","DOI":"10.1128\/JVI.01679-14","article-title":"Influenza A virus acquires enhanced pathogenicity and transmissibility after serial passages in swine","volume":"88","author":"Wei","year":"2014","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7976","DOI":"10.1128\/JVI.00415-06","article-title":"Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice","volume":"80","author":"Zamarin","year":"2006","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1038\/nm1201-1306","article-title":"A novel influenza A virus mitochondrial protein that induces cell death","volume":"7","author":"Chen","year":"2001","journal-title":"Nat. Med."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Conenello, G.M., Zamarin, D., Perrone, L.A., Tumpey, T., and Palese, P. (2007). A single mutation in the PB1-F2 of H5N1 (HK\/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030141"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1126\/science.1222213","article-title":"An overlapping protein-coding region in influenza A virus segment 3 modulates the host response","volume":"337","author":"Jagger","year":"2012","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"12411","DOI":"10.1128\/JVI.01677-12","article-title":"Evolutionary conservation of the PA-X open reading frame in segment 3 of influenza A virus","volume":"86","author":"Shi","year":"2012","journal-title":"J. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8262","DOI":"10.1038\/srep08262","article-title":"The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses","volume":"5","author":"Gao","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.virol.2017.01.015","article-title":"Impacts of different expressions of PA-X protein on 2009 pandemic H1N1 virus replication, pathogenicity and host immune responses","volume":"504","author":"Lee","year":"2017","journal-title":"Virology"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Chaimayo, C., Dunagan, M., Hayashi, T., Santoso, N., and Takimoto, T. (2018). Specificity and functional interplay between influenza virus PA-X and NS1 shutoff activity. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007465"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7131","DOI":"10.1128\/JVI.00954-16","article-title":"Critical Role of the PA-X C-Terminal Domain of Influenza A Virus in Its Subcellular Localization and Shutoff Activity","volume":"90","author":"Hayashi","year":"2016","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"8661","DOI":"10.1128\/JVI.01132-15","article-title":"Mapping of a Region of the PA-X Protein of Influenza A Virus That Is Important for Its Shutoff Activity","volume":"89","author":"Oishi","year":"2015","journal-title":"J. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.virol.2007.08.029","article-title":"Differential role of the influenza A virus polymerase PA subunit for vRNA and cRNA promoter binding","volume":"370","author":"Maier","year":"2008","journal-title":"Virology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1128\/jvi.70.3.1905-1911.1996","article-title":"The amino-terminal one-third of the influenza virus PA protein is responsible for the induction of proteolysis","volume":"70","author":"Zurcher","year":"1996","journal-title":"J. Virol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nature07720","article-title":"Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site","volume":"458","author":"Yuan","year":"2009","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7020","DOI":"10.1128\/JVI.00522-11","article-title":"PA residues in the 2009 H1N1 pandemic influenza virus enhance avian influenza virus polymerase activity in mammalian cells","volume":"85","author":"Bussey","year":"2011","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Lutz, M., Schmierer, J., and Takimoto, T. (2022). Host adaptive mutations in the 2009 H1N1 pandemic influenza A virus PA gene regulate translation efficiency of viral mRNAs via GRSF1. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-04082-5"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Xu, L., Bao, L., Zhou, J., Wang, D., Deng, W., Lv, Q., Ma, Y., Li, F., Sun, H., and Zhan, L. (2011). Genomic polymorphism of the pandemic A (H1N1) influenza viruses correlates with viral replication, virulence, and pathogenicity in vitro and in vivo. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020698"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"12325","DOI":"10.1128\/JVI.01373-09","article-title":"The polymerase acidic protein gene of influenza a virus contributes to pathogenicity in a mouse model","volume":"83","author":"Song","year":"2009","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1128\/JVI.03532-14","article-title":"Mammalian adaptive mutations of the PA protein of highly pathogenic avian H5N1 influenza virus","volume":"89","author":"Yamaji","year":"2015","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e2203919119","DOI":"10.1073\/pnas.2203919119","article-title":"A Eurasian Avian-Like H1n1 Swine Influenza Reassortant Virus Became Pathogenic and Highly Transmissible Due to Mutations in Its Pa Gene","volume":"119","author":"Meng","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1099\/vir.0.018143-0","article-title":"Role of host-specific amino acids in the pathogenicity of avian H5N1 influenza viruses in mice","volume":"91","author":"Kim","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"8607","DOI":"10.1128\/JVI.00159-10","article-title":"Adaptation of pandemic H1N1 influenza viruses in mice","volume":"84","author":"Ilyushina","year":"2010","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"D49","DOI":"10.1016\/j.vaccine.2008.07.039","article-title":"The biology of influenza viruses","volume":"26","author":"Bouvier","year":"2008","journal-title":"Vaccine"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1086\/518792","article-title":"The molecular basis of the pathogenicity of the Dutch highly pathogenic human influenza A H7N7 viruses","volume":"196","author":"Munster","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1126\/science.1125548","article-title":"H5N1 Virus Attachment to Lower Respiratory Tract","volume":"312","author":"Munster","year":"2006","journal-title":"Science"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1086\/652661","article-title":"Quasispecies of the D225G substitution in the hemagglutinin of pandemic influenza A(H1N1) 2009 virus from patients with severe disease in Hong Kong, China","volume":"201","author":"Chen","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"19498","DOI":"10.2807\/ese.15.09.19498-en","article-title":"Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A(H1N1) virus and severe clinical outcome, Norway 2009\u20132010","volume":"15","author":"Kilander","year":"2010","journal-title":"Eurosurveillance"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"863","DOI":"10.3201\/eid1605.091858","article-title":"Transmission of hemagglutinin D222G mutant strain of pandemic (H1N1) 2009 virus","volume":"16","author":"Puzelli","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11802","DOI":"10.1128\/JVI.01136-10","article-title":"Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding","volume":"84","author":"Chutinimitkul","year":"2010","journal-title":"J. Virol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Maurer-Stroh, S., Lee, R.T., Eisenhaber, F., Cui, L., Phuah, S.P., and Lin, R.T. (2010). A new common mutation in the hemagglutinin of the 2009 (H1N1) influenza A virus. PLoS Curr., 2.","DOI":"10.1371\/currents.RRN1162"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"24ra21","DOI":"10.1126\/scitranslmed.3000799","article-title":"Cross-neutralization of 1918 and 2009 influenza viruses: Role of glycans in viral evolution and vaccine design","volume":"2","author":"Wei","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhu, J., Li, Y., Bradley, K.C., Cao, J., Chen, H., Jin, M., and Zhou, H. (2013). Glycosylation on hemagglutinin affects the virulence and pathogenicity of pandemic H1N1\/2009 influenza A virus in mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061397"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"14264","DOI":"10.1073\/pnas.1111000108","article-title":"Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets","volume":"108","author":"Yen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/ncomms1158","article-title":"Differential use of importin-alpha isoforms governs cell tropism and host adaptation of influenza virus","volume":"2","author":"Gabriel","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.virusres.2011.03.022","article-title":"Mutations in PA, NP, and HA of a pandemic (H1N1) 2009 influenza virus contribute to its adaptation to mice","volume":"158","author":"Sakabe","year":"2011","journal-title":"Virus Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"29893","DOI":"10.1074\/jbc.M115.681494","article-title":"Oligomerization and GTP-binding Requirements of MxA for Viral Target Recognition and Antiviral Activity against Influenza A Virus","volume":"290","author":"Nigg","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"13053","DOI":"10.1128\/JVI.02220-13","article-title":"The human interferon-induced MxA protein inhibits early stages of influenza A virus infection by retaining the incoming viral genome in the cytoplasm","volume":"87","author":"Xiao","year":"2013","journal-title":"J. Virol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"10292","DOI":"10.1128\/JVI.00921-07","article-title":"Persistent host markers in pandemic and H5N1 influenza viruses","volume":"81","author":"Finkelstein","year":"2007","journal-title":"J. Virol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Manz, B., Dornfeld, D., Gotz, V., Zell, R., Zimmermann, P., Haller, O., Kochs, G., and Schwemmle, M. (2013). Pandemic influenza A viruses escape from restriction by human MxA through adaptive mutations in the nucleoprotein. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003279"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1128\/JVI.72.7.5493-5501.1998","article-title":"Influenza virus nucleoprotein interacts with influenza virus polymerase proteins","volume":"72","author":"Biswas","year":"1998","journal-title":"J. Virol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1128\/JVI.02749-12","article-title":"Reassortment complements spontaneous mutation in influenza A virus NP and M1 genes to accelerate adaptation to a new host","volume":"87","author":"Ince","year":"2013","journal-title":"J. Virol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1128\/JVI.02642-08","article-title":"Mutational analysis of conserved amino acids in the influenza A virus nucleoprotein","volume":"83","author":"Li","year":"2009","journal-title":"J. Virol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.tvjl.2005.04.014","article-title":"Evidence of the concurrent circulation of H1N2, H1N1 and H3N2 influenza A viruses in densely populated pig areas in Spain","volume":"172","author":"Maldonado","year":"2006","journal-title":"Vet. J."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3389\/fvets.2018.00347","article-title":"Adaptation of Human Influenza Viruses to Swine","volume":"5","author":"Rajao","year":"2018","journal-title":"Front. Vet. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"9221","DOI":"10.1128\/JVI.00697-12","article-title":"Functional balance of the hemagglutinin and neuraminidase activities accompanies the emergence of the 2009 H1N1 influenza pandemic","volume":"86","author":"Xu","year":"2012","journal-title":"J. Virol."},{"key":"ref_126","first-page":"75","article-title":"Evidence for the natural transmission of influenza A virus from wild ducts to swine and its potential importance for man","volume":"59","author":"Pensaert","year":"1981","journal-title":"Bull. World Health Organ."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"11235","DOI":"10.1128\/JVI.05794-11","article-title":"The M segment of the 2009 new pandemic H1N1 influenza virus is critical for its high transmission efficiency in the guinea pig model","volume":"85","author":"Chou","year":"2011","journal-title":"J. Virol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1099\/vir.0.040535-0","article-title":"The neuraminidase and matrix genes of the 2009 pandemic influenza H1N1 virus cooperate functionally to facilitate efficient replication and transmissibility in pigs","volume":"93","author":"Ma","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Lakdawala, S.S., Lamirande, E.W., Suguitan, A.L., Wang, W., Santos, C.P., Vogel, L., Matsuoka, Y., Lindsley, W.G., Jin, H., and Subbarao, K. (2011). Eurasian-origin gene segments contribute to the transmissibility, aerosol release, and morphology of the 2009 pandemic H1N1 influenza virus. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002443"},{"key":"ref_130","unstructured":"Centers for Disease Control and Prevention (2012). Update: Influenza a (H3n2)V Transmission and Guidelines-5 States, 2011. MMWR. Morb. Mortal. Wkly. Rep., 60, 1741\u20131744."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Calderon, B.M., Danzy, S., Delima, G.K., Jacobs, N.T., Ganti, K., Hockman, M.R., Conn, G.L., Lowen, A.C., and Steel, J. (2019). Dysregulation of M segment gene expression contributes to influenza A virus host restriction. PLoS Pathog., 15.","DOI":"10.1101\/599886"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"6691","DOI":"10.1016\/j.vaccine.2017.10.018","article-title":"The M2 protein of live, attenuated influenza vaccine encodes a mutation that reduces replication in human nasal epithelial cells","volume":"35 Pt B","author":"Wohlgemuth","year":"2017","journal-title":"Vaccine"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"7569","DOI":"10.1128\/JVI.00119-14","article-title":"Residue 41 of the Eurasian avian-like swine influenza a virus matrix protein modulates virion filament length and efficiency of contact transmission","volume":"88","author":"Campbell","year":"2014","journal-title":"J. Virol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/BF01309872","article-title":"Specific changes in the M1 protein during adaptation of influenza virus to mouse","volume":"140","author":"Ward","year":"1995","journal-title":"Arch. Virol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1023\/A:1007979709403","article-title":"Virulence of influenza A virus for mouse lung","volume":"14","author":"Ward","year":"1997","journal-title":"Virus Genes."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1128\/jvi.69.1.439-445.1995","article-title":"Hyperphosphorylation of mutant influenza virus matrix protein, M1, causes its retention in the nucleus","volume":"69","author":"Whittaker","year":"1995","journal-title":"J. Virol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1128\/JVI.79.3.1918-1923.2005","article-title":"Attenuating mutations of the matrix gene of influenza A\/WSN\/33 virus","volume":"79","author":"Liu","year":"2005","journal-title":"J. Virol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.virol.2008.11.044","article-title":"Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice","volume":"384","author":"Fan","year":"2009","journal-title":"Virology"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Bialas, K.M., Desmet, E.A., and Takimoto, T. (2012). Specific residues in the 2009 H1N1 swine-origin influenza matrix protein influence virion morphology and efficiency of viral spread in vitro. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050595"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Miotto, O., Heiny, A.T., Albrecht, R., Garcia-Sastre, A., Tan, T.W., August, J.T., and Brusic, V. (2010). Complete-proteome mapping of human influenza A adaptive mutations: Implications for human transmissibility of zoonotic strains. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009025"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3802","DOI":"10.1128\/JVI.03607-13","article-title":"The M segment of the 2009 pandemic influenza virus confers increased neuraminidase activity, filamentous morphology, and efficient contact transmissibility to A\/Puerto Rico\/8\/1934-based reassortant viruses","volume":"88","author":"Campbell","year":"2014","journal-title":"J. Virol."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Seladi-Schulman, J., Campbell, P.J., Suppiah, S., Steel, J., and Lowen, A.C. (2014). Filament-producing mutants of influenza A\/Puerto Rico\/8\/1934 (H1N1) virus have higher neuraminidase activities than the spherical wild-type. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112462"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1086\/518936","article-title":"Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide","volume":"196","author":"Deyde","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cplett.2009.12.037","article-title":"Computational 3D structures of drug-targeting proteins in the 2009-H1N1 influenza A virus","volume":"485","author":"Du","year":"2010","journal-title":"Chem Phys Lett"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1099\/vir.0.2008\/004606-0","article-title":"The multifunctional NS1 protein of influenza A viruses","volume":"89","author":"Hale","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/nm757","article-title":"Lethal H5N1 influenza viruses escape host anti-viral cytokine responses","volume":"8","author":"Seo","year":"2002","journal-title":"Nat. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e00721-17","DOI":"10.1128\/JVI.00721-17","article-title":"Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses","volume":"91","author":"Clark","year":"2017","journal-title":"J. Virol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"13093","DOI":"10.1073\/pnas.0805213105","article-title":"Structural basis for suppression of a host antiviral response by influenza A virus","volume":"105","author":"Das","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"7011","DOI":"10.1128\/JVI.02581-06","article-title":"Multiple anti-interferon actions of the influenza A virus NS1 protein","volume":"81","author":"Kochs","year":"2007","journal-title":"J. Virol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/S1097-2765(00)80099-4","article-title":"Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3\u2032 end formation of cellular pre-mRNAs","volume":"1","author":"Nemeroff","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0042-6822(02)00127-7","article-title":"Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3\u2032 end processing of cellular pre-mRNAS","volume":"307","author":"Noah","year":"2003","journal-title":"Virology"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1073\/pnas.0800482105","article-title":"A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity","volume":"105","author":"Jackson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1099\/jgv.0.000542","article-title":"Identification of specific residues in avian influenza A virus NS1 that enhance viral replication and pathogenicity in mammalian systems","volume":"97","author":"Kanrai","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"6909","DOI":"10.1128\/JVI.00081-10","article-title":"Inefficient control of host gene expression by the 2009 pandemic H1N1 influenza A virus NS1 protein","volume":"84","author":"Hale","year":"2010","journal-title":"J. Virol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/1743-422X-10-243","article-title":"Influenza A\/Hong Kong\/156\/1997(H5N1) virus NS1 gene mutations F103L and M106I both increase IFN antagonism, virulence and cytoplasmic localization but differ in binding to RIG-I and CPSF30","volume":"10","author":"Dankar","year":"2013","journal-title":"Virol. J."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/ncomms1804","article-title":"Adaptive mutations in NEP compensate for defective H5N1 RNA replication in cultured human cells","volume":"3","author":"Manz","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1128\/JVI.01698-07","article-title":"A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice","volume":"82","author":"Jiao","year":"2008","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/9\/1959\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:54:16Z","timestamp":1760129656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/9\/1959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,20]]},"references-count":157,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["v15091959"],"URL":"https:\/\/doi.org\/10.3390\/v15091959","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,20]]}}}