{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:05:27Z","timestamp":1791482727276,"version":"4.3.4"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T00:00:00Z","timestamp":1577923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of the People\u2019s Republic of China","award":["2016YFC1201603"],"award-info":[{"award-number":["2016YFC1201603"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Swine influenza virus causes a substantial disease burden to swine populations worldwide and poses an imminent threat to the swine industry and humans. Given its importance, we characterized two swine influenza viruses isolated from Shandong, China. The homology and phylogenetic analyses showed that all eight gene segments of A\/swine\/Shandong\/AV1522\/2011(H1N1) were closely related to A\/Maryland\/12\/1991(H1N1) circulating in North America. The HA, NA, M, and NS genes of the isolate were also confirmed to have a high homology to A\/swine\/Hubei\/02\/2008(H1N1) which appeared in China in 2008, and the virus was clustered into the classical swine lineage. The gene segments of A\/swine\/Shandong\/AV1523\/2011(H1N1) were highly homologous to the early human H1N1 and H2N2 influenza viruses, except for the HA gene, and the virus was a reassortant H1N1 virus containing genes from the classical swine (HA) and human (NA, PB2, PB1, PA, NP, M, and NS) lineages. Both the viruses could cause lethal infection and replicate efficiently in the lungs, brains, spleens, and kidneys of mice. Histopathological examinations showed that AV1522 and AV1523 viruses caused a spectrum of marked pneumonia and meningoencephalitis according to the duration of infection, demonstrating a progression of respiratory disease and neurological disease over the course of infection that ultimately resulted in lethality for the infected mice. The changes in the pathogenicity of swine influenza viruses to mammals, accompanied with the continuous reassortment and evolution of the viruses, highlights the importance of ongoing epidemiological investigation.<\/jats:p>","DOI":"10.3390\/v12010055","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T04:43:03Z","timestamp":1578026583000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification, Genetic Analysis, and Pathogenicity of Classical Swine H1N1 and Human-Swine Reassortant H1N1 Influenza Viruses from Pigs in China"],"prefix":"10.3390","volume":"12","author":[{"given":"Yafen","family":"Song","sequence":"first","affiliation":[{"name":"Department of Veterinary Culture Collection, China Institute of Veterinary Drug Control, 8 Nandajie, Zhongguancun, Haidian District, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Culture Collection, China Institute of Veterinary Drug Control, 8 Nandajie, Zhongguancun, Haidian District, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Culture Collection, China Institute of Veterinary Drug Control, 8 Nandajie, Zhongguancun, Haidian District, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Culture Collection, China Institute of Veterinary Drug Control, 8 Nandajie, Zhongguancun, Haidian District, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Culture Collection, China Institute of Veterinary Drug Control, 8 Nandajie, Zhongguancun, Haidian District, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Culture Collection, China Institute of Veterinary Drug Control, 8 Nandajie, Zhongguancun, Haidian District, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Culture Collection, China Institute of Veterinary Drug Control, 8 Nandajie, Zhongguancun, Haidian District, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghuai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Culture Collection, China Institute of Veterinary Drug Control, 8 Nandajie, Zhongguancun, Haidian District, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taozhen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Culture Collection, China Institute of Veterinary Drug Control, 8 Nandajie, Zhongguancun, Haidian District, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5637","DOI":"10.1016\/j.vaccine.2006.10.051","article-title":"An overview of the epidemiology of avian influenza","volume":"25","author":"Alexander","year":"2007","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/nrmicro.2017.146","article-title":"The evolution of seasonal influenza viruses","volume":"16","author":"Petrova","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Baudon, E., Peyre, M., Peiris, M., and Cowling, B.J. (2017). Epidemiological features of influenza circulation in swine populations: A systematic review and meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179044"},{"key":"ref_4","first-page":"133","article-title":"History and epidemiology of Swine influenza in Europe","volume":"370","author":"Brown","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1128\/JCM.40.3.1073-1079.2002","article-title":"Genetic characterization of H1N2 influenza A viruses isolated from pigs throughout the United States","volume":"40","author":"Karasin","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0168-1702(00)00154-4","article-title":"Genetic characterization of H3N2 influenza viruses isolated from pigs in North America, 1977\u20131999: Evidence for wholly human and reassortant virus genotypes","volume":"68","author":"Karasin","year":"2000","journal-title":"Virus Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/s11262-009-0386-6","article-title":"Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States","volume":"39","author":"Vincent","year":"2009","journal-title":"Virus Genes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.virusres.2004.02.015","article-title":"Multiple lineages of antigenically and genetically diverse influenza A virus co-circulate in the United States swine population","volume":"103","author":"Webby","year":"2004","journal-title":"Virus Res."},{"key":"ref_9","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_10","first-page":"57","article-title":"History of Swine influenza viruses in Asia","volume":"370","author":"Zhu","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-018-0002-y","article-title":"Influenza","volume":"4","author":"Krammer","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1750-2659.2009.00096.x","article-title":"Diversity of influenza viruses in swine and the emergence of a novel human pandemic influenza A (H1N1)","volume":"3","author":"Webster","year":"2009","journal-title":"Influenza Other Respir Viruses"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.coviro.2012.03.003","article-title":"The role of receptor binding specificity in interspecies transmission of influenza viruses","volume":"2","author":"Imai","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_15","first-page":"158","article-title":"The pig as a mixing vessel for influenza viruses: Human and veterinary implications","volume":"3","author":"Ma","year":"2008","journal-title":"J. Mol. Genet. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jcv.2009.06.006","article-title":"Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans","volume":"45","author":"Peiris","year":"2009","journal-title":"J. Clin. Virol."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1128\/JCM.02386-07","article-title":"Subtyping of avian influenza viruses H1 to H15 on the basis of hemagglutinin genes by PCR assay and molecular determination of pathogenic potential","volume":"46","author":"Tsukamoto","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1128\/JCM.02366-08","article-title":"Use of reverse transcriptase PCR to subtype N1 to N9 neuraminidase genes of avian influenza viruses","volume":"47","author":"Tsukamoto","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature10004","article-title":"Long-term evolution and transmission dynamics of swine influenza A virus","volume":"473","author":"Vijaykrishna","year":"2011","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0092-8674(82)90135-0","article-title":"The antigenic structure of the influenza virus A\/PR\/8\/34 hemagglutinin (H1 subtype)","volume":"31","author":"Caton","year":"1982","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/289373a0","article-title":"Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation","volume":"289","author":"Wiley","year":"1981","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2147\/IDR.S105473","article-title":"Drug resistance in influenza A virus: The epidemiology and management","volume":"10","author":"Hussain","year":"2017","journal-title":"Infect. Drug Resist."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.tips.2013.08.003","article-title":"Structural and energetic analysis of drug inhibition of the influenza A M2 proton channel","volume":"34","author":"Gu","year":"2013","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1084\/jem.20051938","article-title":"The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A\/Vietnam\/1203\/04","volume":"203","author":"Salomon","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41426-018-0073-6","article-title":"Substitution of D701N in the PB2 protein could enhance the viral replication and pathogenicity of Eurasian avian-like H1N1 swine influenza viruses","volume":"7","author":"Liu","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_28","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_29","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."},{"key":"ref_30","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_31","first-page":"468","article-title":"A practical method for field diagnosis of swine diseases","volume":"14","author":"Koen","year":"1919","journal-title":"Am. J. Vet. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.meegid.2012.09.021","article-title":"Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China","volume":"13","author":"Chen","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00275-16","DOI":"10.1128\/mSphere.00275-16","article-title":"A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses","volume":"1","author":"Anderson","year":"2016","journal-title":"MSphere"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10864","DOI":"10.1128\/JVI.01327-14","article-title":"Expansion of genotypic diversity and establishment of 2009 H1N1 pandemic-origin internal genes in pigs in China","volume":"88","author":"Liang","year":"2014","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.virusres.2008.11.008","article-title":"Further evidence for infection of pigs with human-like H1N1 influenza viruses in China","volume":"140","author":"Yu","year":"2009","journal-title":"Virus Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0378-1135(00)00164-4","article-title":"The epidemiology and evolution of influenza viruses in pigs","volume":"74","author":"Brown","year":"2000","journal-title":"Vet. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1128\/JCM.44.3.1123-1126.2006","article-title":"Identification of human H1N2 and human-swine reassortant H1N2 and H1N1 influenza A viruses among pigs in Ontario, Canada (2003 to 2005)","volume":"44","author":"Karasin","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jcv.2010.07.018","article-title":"Genetic correlation between current circulating H1N1 swine and human influenza viruses","volume":"49","author":"Lu","year":"2010","journal-title":"J. Clin. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.1119392","article-title":"Characterization of the reconstructed 1918 Spanish influenza pandemic virus","volume":"310","author":"Tumpey","year":"2005","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e01444-18","DOI":"10.1128\/JVI.01444-18","article-title":"Comparative In Vitro and In Vivo Analysis of H1N1 and H1N2 Variant Influenza Viruses Isolated from Humans between 2011 and 2016","volume":"92","author":"Pappas","year":"2018","journal-title":"J. Virol."},{"key":"ref_41","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_42","doi-asserted-by":"crossref","first-page":"4194","DOI":"10.1128\/JVI.02742-09","article-title":"Pathogenesis of pandemic influenza A (H1N1) and triple-reassortant swine influenza A (H1) viruses in mice","volume":"84","author":"Belser","year":"2010","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13849","DOI":"10.1073\/pnas.212519699","article-title":"Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus","volume":"99","author":"Tumpey","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.virol.2009.08.021","article-title":"An early \u2018classical\u2019 swine H1N1 influenza virus shows similar pathogenicity to the 1918 pandemic virus in ferrets and mice","volume":"393","author":"Memoli","year":"2009","journal-title":"Virology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.3201\/eid2211.160181","article-title":"Reassortant Eurasian Avian-Like Influenza A(H1N1) Virus from a Severely Ill Child, Hunan Province, China, 2015","volume":"22","author":"Zhu","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.1128\/jvi.64.9.4523-4533.1990","article-title":"Increased virulence of a mouse-adapted variant of influenza A\/FM\/1\/47 virus is controlled by mutations in genome segments 4, 5, 7, and 8","volume":"64","author":"Brown","year":"1990","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nature02951","article-title":"Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus","volume":"431","author":"Kobasa","year":"2004","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1073\/pnas.0711815105","article-title":"Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus","volume":"105","author":"Pappas","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","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_50","unstructured":"(2019, January 09). The Food and Agricultural Trade Dataset. Available online: http:\/\/www.fao.org\/faostat\/en\/#data\/TA."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/1\/55\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:18:46Z","timestamp":1760361526000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/1\/55"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,2]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["v12010055"],"URL":"https:\/\/doi.org\/10.3390\/v12010055","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,2]]}}}