{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T21:10:05Z","timestamp":1776978605240,"version":"3.51.4"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31830097"],"award-info":[{"award-number":["31830097"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31672586"],"award-info":[{"award-number":["31672586"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015956","name":"Key Research and Development Program of Guangdong Province","doi-asserted-by":"publisher","award":["2019B020218004"],"award-info":[{"award-number":["2019B020218004"]}],"id":[{"id":"10.13039\/501100015956","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Earmarked Found for China Agriculture Research System","award":["CARS-41-G16"],"award-info":[{"award-number":["CARS-41-G16"]}]},{"name":"Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme","award":["2018, Wenbao Qi"],"award-info":[{"award-number":["2018, Wenbao Qi"]}]},{"name":"Young Scholars of Yangtze River Scholar Professor Program","award":["2019, Wenbao Qi"],"award-info":[{"award-number":["2019, Wenbao Qi"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Since it firstly emerged in China in 2013, clade 2.3.4.4 H5N6 highly pathogenic avian influenza viruses (HPAIVs) has rapidly replaced predominant H5N1 to become the dominant H5 subtype in China, especially in ducks. Not only endemic in China, it also crossed the geographical barrier and emerged in South Korea, Japan, and Europe. Here, we analyzed the genetic properties of the clade 2.3.4.4 H5N6 HPAIVs with full genome sequences available online together with our own isolates. Phylogenetic analysis showed that clade 2.3.4.4 H5N6 HPAIVs continuously reassorted with local H5, H6, and H7N9\/H9N2. Species analysis reveals that aquatic poultry and migratory birds became the dominant hosts of H5N6. Adaption to aquatic poultry might help clade 2.3.4.4 H5N6 better adapt to migratory birds, thus enabling it to become endemic in China. Besides, migratory birds might help clade 2.3.4.4 H5N6 transmit all over the world. Clade 2.3.4.4 H5N6 HPAIVs also showed a preference for \u03b12,6-SA receptors when compared to other avian origin influenza viruses. Experiments in vitro and in vivo revealed that clade 2.3.4.4 H5N6 HPAIVs exhibited high replication efficiency in both avian and mammal cells, and it also showed high pathogenicity in both mice and chickens, demonstrating high risk to public health. Considering all the factors together, adaption to aquatic poultry and migratory birds helps clade 2.3.4.4 H5N6 overcome the geographical isolation, and it has potential to be the next influenza pandemic in the world, making it worthy of our attention.<\/jats:p>","DOI":"10.3390\/pathogens9080670","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T09:22:31Z","timestamp":1597828951000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Continuous Reassortment of Clade 2.3.4.4 H5N6 Highly Pathogenetic Avian Influenza Viruses Demonstrating High Risk to Public Health"],"prefix":"10.3390","volume":"9","author":[{"given":"Huanan","family":"Li","sequence":"first","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China"},{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Xiaqiu Animal Husbandry &amp; Veterinary Station, Yantai 261400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Guo","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinchao","family":"Xing","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Xu","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lele","family":"Liu","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8780-1497","authenticated-orcid":false,"given":"Jiahao","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbao","family":"Qi","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China"},{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixin","family":"Jia","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China"},{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Liao","sequence":"additional","affiliation":[{"name":"National Avian Influenza Para-Reference Laboratory (Guangzhou), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China"},{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China"},{"name":"National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou 510642, China"},{"name":"Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Qi, X., Cui, L., Yu, H., Ge, Y., and Tang, F. (2014). Whole-Genome Sequence of a Reassortant H5N6 Avian Influenza Virus Isolated from a Live Poultry Market in China, 2013. Genome Announc., 2.","DOI":"10.1128\/genomeA.00706-14"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.meegid.2015.01.019","article-title":"Novel reassortant highly pathogenic H5N6 avian influenza viruses in poultry in China","volume":"31","author":"Wu","year":"2015","journal-title":"Infect. Genet. Evol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"511","DOI":"10.3201\/eid2103.141488","article-title":"Reassortant highly pathogenic influenza A(H5N6) virus in Laos","volume":"21","author":"Wong","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"#cr-split#-ref_4.1","unstructured":"Nguyen, D.T., Jang, Y., Nguyen, T.D., Jones, J., Shepard, S.S., Yang, H., Gerloff, N., Fabrizio, T., Nguyen, L.V., and Inui, K. (2017). Shifting Clade Distribution, Reassortment, and Emergence of New Subtypes of Highly Pathogenic Avian Influenza A"},{"key":"#cr-split#-ref_4.2","unstructured":"(H5) Viruses Collected from Vietnamese Poultry from 2012 to 2015. J. Virol., 91."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"822","DOI":"10.3201\/eid2305.161905","article-title":"Reassortant Clade 2.3.4.4 Avian Influenza A(H5N6) Virus in a Wild Mandarin Duck, South Korea, 2016","volume":"23","author":"Kwon","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3201\/eid2304.161957","article-title":"Characterization of Highly Pathogenic Avian Influenza Virus A(H5N6), Japan, November 2016","volume":"23","author":"Okamatsu","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Beerens, N., Koch, G., Heutink, R., Harders, F., Vries, D.P.E., Ho, C., Bossers, A., and Elbers, A. (2018). Novel Highly Pathogenic Avian Influenza A(H5N6) Virus in the Netherlands, December 2017. Emerg. Infect. Dis., 24.","DOI":"10.3201\/eid2404.172124"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.chom.2016.10.022","article-title":"Genesis, Evolution and Prevalence of H5N6 Avian Influenza Viruses in China","volume":"20","author":"Bi","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.meegid.2015.08.017","article-title":"Genetic and biological characterization of two novel reassortant H5N6 swine influenza viruses in mice and chickens","volume":"36","author":"Li","year":"2015","journal-title":"Infect. Genet. Evol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.meegid.2016.03.010","article-title":"Clinical, epidemiological and virological characteristics of the first detected human case of avian influenza A(H5N6) virus","volume":"40","author":"Zhang","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1099\/vir.0.023168-0","article-title":"Molecular epidemiological surveys of H5 subtype highly pathogenic avian influenza viruses in poultry in China during 2007-2009","volume":"91","author":"Jiang","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8389","DOI":"10.1128\/JVI.00413-10","article-title":"Continued evolution of H5N1 influenza viruses in wild birds, domestic poultry, and humans in China from 2004 to 2009","volume":"84","author":"Li","year":"2010","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/cr.2009.124","article-title":"H5N1 influenza viruses: Outbreaks and biological properties","volume":"20","author":"Neumann","year":"2010","journal-title":"Cell Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8671","DOI":"10.1128\/JVI.01034-15","article-title":"Epidemiology, Evolution, and Recent Outbreaks of Avian Influenza Virus in China","volume":"89","author":"Su","year":"2015","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10402","DOI":"10.1128\/JVI.01157-07","article-title":"Establishment of influenza A virus (H6N1) in minor poultry species in southern China","volume":"81","author":"Cheung","year":"2007","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6075","DOI":"10.1128\/JVI.06389-11","article-title":"Establishment and lineage replacement of H6 influenza viruses in domestic ducks in southern China","volume":"86","author":"Huang","year":"2012","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S2213-2600(13)70221-2","article-title":"Human infection with avian influenza A H6N1 virus: An epidemiological analysis","volume":"1","author":"Wei","year":"2013","journal-title":"Lancet Respir. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wu, Z.Q., Zhang, Y., Zhao, N., Yu, Z., Pan, H., Chan, T.C., Zhang, Z.R., and Liu, S.L. (2017). Comparative Epidemiology of Human Fatal Infections with Novel, High (H5N6 and H5N1) and Low (H7N9 and H9N2) Pathogenicity Avian Influenza A Viruses. Int. J. Environ. Res. Public Health, 14.","DOI":"10.3390\/ijerph14030263"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJMoa1304459","article-title":"Human infection with a novel avian-origin influenza A (H7N9) virus","volume":"368","author":"Gao","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S0140-6736(14)60111-2","article-title":"Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: A descriptive study","volume":"383","author":"Chen","year":"2014","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s13238-014-0084-6","article-title":"Continuous reassortments with local chicken H9N2 virus underlie the human-infecting influenza A (H7N9) virus in the new influenza season, Guangdong, China","volume":"5","author":"Qi","year":"2014","journal-title":"Protein Cell"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Qi, W., Zhou, X., Shi, W., Huang, L., Xia, W., Liu, D., Li, H., Chen, S., Lei, F., and Cao, L. (2014). Genesis of the novel human-infecting influenza A(H10N8) virus and potential genetic diversity of the virus in poultry, China. Euro Surveill., 19.","DOI":"10.2807\/1560-7917.ES2014.19.25.20841"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, X., Shi, J., Guo, J., Deng, G., Zhang, Q., Wang, J., He, X., Wang, K., Chen, J., and Li, Y. (2014). Genetics, receptor binding property, and transmissibility in mammals of naturally isolated H9N2 Avian Influenza viruses. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004508"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1099\/vir.0.021402-0","article-title":"Viral reassortment and transmission after co-infection of pigs with classical H1N1 and triple-reassortant H3N2 swine influenza viruses","volume":"91","author":"Ma","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.vetmic.2018.06.011","article-title":"High frequency of reassortment after co-infection of chickens with the H4N6 and H9N2 influenza A viruses and the biological characteristics of the reassortants","volume":"222","author":"Li","year":"2018","journal-title":"Vet. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"427","DOI":"10.18388\/abp.2014_1860","article-title":"In vivo reassortment of influenza viruses","volume":"61","author":"Urbaniak","year":"2014","journal-title":"Acta Biochim. Pol."},{"key":"ref_27","first-page":"e02199","article-title":"Genesis and Dissemination of Highly Pathogenic H5N6 Avian Influenza Viruses","volume":"91","author":"Yang","year":"2017","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1111\/tbed.12861","article-title":"Emergence and spread of highly pathogenic avian influenza A(H5N8) in Europe in 2016-2017","volume":"65","author":"Napp","year":"2018","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.3201\/eid2006.140233","article-title":"Novel reassortant influenza A(H5N8) viruses, South Korea, 2014","volume":"20","author":"Lee","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.vetmic.2012.12.025","article-title":"Characterization of three H5N5 and one H5N8 highly pathogenic avian influenza viruses in China","volume":"163","author":"Zhao","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2807\/1560-7917.ES2015.20.20.21132","article-title":"Genetic diversity of highly pathogenic H5N8 avian influenza viruses at a single overwintering site of migratory birds in Japan, 2014\/15","volume":"20","author":"Ozawa","year":"2015","journal-title":"Eurosurveillance"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e934","DOI":"10.7717\/peerj.934","article-title":"The European and Japanese outbreaks of H5N8 derive from a single source population providing evidence for the dispersal along the long distance bird migratory flyways","volume":"3","author":"Dalby","year":"2015","journal-title":"PeerJ"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"886","DOI":"10.3201\/eid2105.142020","article-title":"Novel Eurasian highly pathogenic avian influenza A H5 viruses in wild birds, Washington, USA, 2014","volume":"21","author":"Ip","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9484","DOI":"10.1038\/srep09484","article-title":"Reassortant highly pathogenic influenza A H5N2 virus containing gene segments related to Eurasian H5N8 in British Columbia, Canada, 2014","volume":"5","author":"Pasick","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17430","DOI":"10.1021\/ja904052q","article-title":"Mechanism of Glycan Receptor Recognition and Specificity Switch for Avian, Swine, and Human Adapted Influenza Virus Hemagglutinins: A Molecular Dynamics Perspective","volume":"131","author":"Newhouse","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11181","DOI":"10.1073\/pnas.201401198","article-title":"X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs","volume":"98","author":"Ha","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1006\/viro.1997.8958","article-title":"Studies of the binding properties of influenza hemagglutinin receptor-site mutants","volume":"241","author":"Martin","year":"1998","journal-title":"Virology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7626","DOI":"10.1128\/JVI.72.9.7626-7631.1998","article-title":"The role of influenza A virus hemagglutinin residues 226 and 228 in receptor specificity and host range restriction","volume":"72","author":"Vines","year":"1998","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1126\/science.1062882","article-title":"Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses","volume":"293","author":"Hatta","year":"2001","journal-title":"Science"},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"8735","DOI":"10.1128\/JVI.00422-14","article-title":"PB2 mutations D701N and S714R promote adaptation of an influenza H5N1 virus to a mammalian host","volume":"88","author":"Otte","year":"2014","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19474","DOI":"10.1038\/srep19474","article-title":"PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses","volume":"6","author":"Xiao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"842","DOI":"10.3201\/eid2105.141927","article-title":"Rapid Emergence of Highly Pathogenic Avian Influenza Subtypes from a Subtype H5N1 Hemagglutinin Variant","volume":"21","author":"Guo","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1007\/s007050170002","article-title":"Universal primer set for the full-length amplification of all influenza A viruses","volume":"146","author":"Hoffmann","year":"2001","journal-title":"Arch. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: Multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: A fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies","volume":"32","author":"Nguyen","year":"2015","journal-title":"Mol. Biol. Evol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1093\/molbev\/mst024","article-title":"Ultrafast approximation for phylogenetic bootstrap","volume":"30","author":"Minh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jviromet.2008.06.019","article-title":"Evaluation of chicken-origin (DF-1) and quail-origin (QT-6) fibroblast cell lines for replication of avian influenza viruses","volume":"153","author":"Lee","year":"2008","journal-title":"J. Virol. Methods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0305-0491(00)00213-3","article-title":"Differential expression of sialic acid on porcine organs during the maturation process","volume":"126","author":"Vallejo","year":"2000","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11434","DOI":"10.1038\/srep11434","article-title":"In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses","volume":"5","author":"Schmier","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3389\/fmicb.2017.01084","article-title":"Biological Characterizations of H5Nx Avian Influenza Viruses Embodying Different Neuraminidases","volume":"8","author":"Yu","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.3389\/fmicb.2018.01088","article-title":"The Appropriate Combination of Hemagglutinin and Neuraminidase Prompts the Predominant H5N6 Highly Pathogenic Avian Influenza Virus in Birds","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.virol.2008.07.038","article-title":"The development and genetic diversity of H5N1 influenza virus in China, 1996\u20132006","volume":"380","author":"Duan","year":"2008","journal-title":"Virology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1128\/JVI.02510-13","article-title":"Comparative virus replication and host innate responses in human cells infected with three prevalent clades (2.3.4, 2.3.2, and 7) of highly pathogenic avian influenza H5N1 viruses","volume":"88","author":"Sun","year":"2014","journal-title":"J. Virol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/8\/670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:02:45Z","timestamp":1760176965000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/8\/670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,18]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["pathogens9080670"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9080670","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,18]]}}}