{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:42:12Z","timestamp":1780342932504,"version":"3.54.1"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Microbiology"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.vetmic.2022.109615","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T22:29:37Z","timestamp":1670279377000},"page":"109615","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Synergistic HA and NS mutations enhanced the virulence of a mouse-adapted H1N1 influenza A virus"],"prefix":"10.1016","volume":"276","author":[{"given":"Min","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaohui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyuan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongqiang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiancai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzhang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6720-353X","authenticated-orcid":false,"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.vetmic.2022.109615_bib1","doi-asserted-by":"crossref","first-page":"6883","DOI":"10.1073\/pnas.111165798","article-title":"Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: identification of functional themes","volume":"98","author":"Brown","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.vetmic.2022.109615_bib2","first-page":"9","article-title":"Emergence and evolution of novel reassortant influenza a viruses in canines in Southern China","author":"Chen","year":"2018","journal-title":"mBio"},{"key":"10.1016\/j.vetmic.2022.109615_bib3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.virol.2010.05.024","article-title":"Dogs are highly susceptible to H5N1 avian influenza virus","volume":"405","author":"Chen","year":"2010","journal-title":"Virology"},{"key":"10.1016\/j.vetmic.2022.109615_bib4","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1126\/science.1117950","article-title":"Transmission of equine influenza virus to dogs","volume":"310","author":"Crawford","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.vetmic.2022.109615_bib5","doi-asserted-by":"crossref","first-page":"5868","DOI":"10.1074\/jbc.M110.193557","article-title":"Only two residues are responsible for the dramatic difference in receptor binding between swine and new pandemic H1 hemagglutinin","volume":"286","author":"de Vries","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.vetmic.2022.109615_bib6","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2021.693204","article-title":"Molecular evolution of the influenza a virus non-structural protein 1 in interspecies transmission and adaptation","volume":"12","author":"Evseev","year":"2021","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.vetmic.2022.109615_bib7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0031839","article-title":"Multifunctional adaptive NS1 mutations are selected upon human influenza virus evolution in the mouse","volume":"7","author":"Forbes","year":"2012","journal-title":"PloS One"},{"key":"10.1016\/j.vetmic.2022.109615_bib8","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":"10.1016\/j.vetmic.2022.109615_bib9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000709","article-title":"Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host","volume":"5","author":"Gao","year":"2009","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.vetmic.2022.109615_bib10","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":"10.1016\/j.vetmic.2022.109615_bib11","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00430-014-0349-y","article-title":"Crucial role of PA in virus life cycle and host adaptation of influenza A virus","volume":"204","author":"Hu","year":"2015","journal-title":"Med. Microbiol. Immunol."},{"key":"10.1016\/j.vetmic.2022.109615_bib12","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":"10.1016\/j.vetmic.2022.109615_bib13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00705-009-0535-1","article-title":"Readaptation of a low-virulence influenza H9 escape mutant in mice: the role of changes in hemagglutinin as revealed by site-specific mutagenesis","volume":"155","author":"Ilyushina","year":"2010","journal-title":"Arch. Virol."},{"key":"10.1016\/j.vetmic.2022.109615_bib14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0017616","article-title":"A single base-pair change in 2009 H1N1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets","volume":"6","author":"Jayaraman","year":"2011","journal-title":"PloS One"},{"key":"10.1016\/j.vetmic.2022.109615_bib15","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":"10.1016\/j.vetmic.2022.109615_bib16","doi-asserted-by":"crossref","first-page":"11599","DOI":"10.1128\/JVI.01393-08","article-title":"Experimental evolution of human influenza virus H3 hemagglutinin in the mouse lung identifies adaptive regions in HA1 and HA2","volume":"82","author":"Keleta","year":"2008","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2022.109615_bib17","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1080\/22221751.2021.1997340","article-title":"A single-amino-acid mutation at position 225 in hemagglutinin attenuates H5N6 influenza virus in mice","volume":"10","author":"Kong","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"10.1016\/j.vetmic.2022.109615_bib18","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.3201\/eid2112.141229","article-title":"Influenza A(H6N1) Virus in Dogs, Taiwan","volume":"21","author":"Lin","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"10.1016\/j.vetmic.2022.109615_bib19","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1126\/science.1177238","article-title":"Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice","volume":"325","author":"Maines","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.vetmic.2022.109615_bib20","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":"10.1016\/j.vetmic.2022.109615_bib21","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":"10.1016\/j.vetmic.2022.109615_bib22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003019","article-title":"Emerging roles for the influenza A virus nuclear export protein (NEP)","volume":"8","author":"Paterson","year":"2012","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.vetmic.2022.109615_bib23","doi-asserted-by":"crossref","DOI":"10.1038\/emi.2012.38","article-title":"Adaptive mutation in influenza A virus non-structural gene is linked to host switching and induces a novel protein by alternative splicing","volume":"1","author":"Selman","year":"2012","journal-title":"Emerg. Microbes Infect."},{"key":"10.1016\/j.vetmic.2022.109615_bib24","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":"10.1016\/j.vetmic.2022.109615_bib25","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1126\/science.1124513","article-title":"Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus","volume":"312","author":"Stevens","year":"2006","journal-title":"Science"},{"key":"10.1016\/j.vetmic.2022.109615_bib26","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":"10.1016\/j.vetmic.2022.109615_bib27","doi-asserted-by":"crossref","first-page":"17204","DOI":"10.1073\/pnas.1921186117","article-title":"Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection","volume":"117","author":"Sun","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.vetmic.2022.109615_bib28","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.meegid.2013.10.012","article-title":"Evidence of avian-like H9N2 influenza A virus among dogs in Guangxi, China","volume":"20","author":"Sun","year":"2013","journal-title":"Infect., Genet. Evol.: J. Mol. Epidemiol. Evolut. Genet. Infect. Dis."},{"key":"10.1016\/j.vetmic.2022.109615_bib29","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.chom.2010.05.009","article-title":"Influenza virus evolution, host adaptation, and pandemic formation","volume":"7","author":"Taubenberger","year":"2010","journal-title":"Cell host Microbe"},{"key":"10.1016\/j.vetmic.2022.109615_bib30","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1126\/science.1136212","article-title":"A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission","volume":"315","author":"Tumpey","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.vetmic.2022.109615_bib31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0025755","article-title":"A single amino acid in the HA of pH1N1 2009 influenza virus affects cell tropism in human airway epithelium, but not transmission in ferrets","volume":"6","author":"van Doremalen","year":"2011","journal-title":"PloS One"},{"key":"10.1016\/j.vetmic.2022.109615_bib32","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1080\/22221751.2019.1637284","article-title":"Characterization of swine-origin H1N1 canine influenza viruses","volume":"8","author":"Wang","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"10.1016\/j.vetmic.2022.109615_bib33","first-page":"91","article-title":"A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs","author":"Wang","year":"2017","journal-title":"J. Virol."},{"key":"10.1016\/j.vetmic.2022.109615_bib34","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":"10.1016\/j.vetmic.2022.109615_bib35","first-page":"11","article-title":"Canine and Feline Influenza","author":"Wasik","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.vetmic.2022.109615_bib36","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1099\/vir.0.054692-0","article-title":"Mutation tryptophan to leucine at position 222 of haemagglutinin could facilitate H3N2 influenza A virus infection in dogs","volume":"94","author":"Yang","year":"2013","journal-title":"J. Gen. Virol."},{"key":"10.1016\/j.vetmic.2022.109615_bib37","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.vetmic.2011.08.017","article-title":"Genetic characterization of a novel influenza A virus H5N2 isolated from a dog in China","volume":"155","author":"Zhan","year":"2012","journal-title":"Vet. Microbiol."},{"key":"10.1016\/j.vetmic.2022.109615_bib38","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1258\/ebm.2010.010071","article-title":"D225G mutation in hemagglutinin of pandemic influenza H1N1 (2009) virus enhances virulence in mice","volume":"235","author":"Zheng","year":"2010","journal-title":"Exp. Biol. Med."},{"key":"10.1016\/j.vetmic.2022.109615_bib39","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":"10.1016\/j.vetmic.2022.109615_bib40","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1128\/JVI.03395-14","article-title":"Origins and evolutionary dynamics of H3N2 canine influenza virus","volume":"89","author":"Zhu","year":"2015","journal-title":"J. Virol."}],"updated-by":[{"DOI":"10.1016\/j.vetmic.2024.110135","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000}}],"container-title":["Veterinary Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S037811352200284X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S037811352200284X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T01:21:01Z","timestamp":1707787261000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S037811352200284X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":40,"alternative-id":["S037811352200284X"],"URL":"https:\/\/doi.org\/10.1016\/j.vetmic.2022.109615","relation":{"erratum":[{"id-type":"doi","id":"10.1016\/j.vetmic.2024.110135","asserted-by":"object"}]},"ISSN":["0378-1135"],"issn-type":[{"value":"0378-1135","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synergistic HA and NS mutations enhanced the virulence of a mouse-adapted H1N1 influenza A virus","name":"articletitle","label":"Article Title"},{"value":"Veterinary Microbiology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.vetmic.2022.109615","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"109615"}}