{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:27:18Z","timestamp":1785421638348,"version":"3.56.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32273037, 32102636"],"award-info":[{"award-number":["32273037, 32102636"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Major Project of Basic and Applied Basic Research","award":["2020B0301030007"],"award-info":[{"award-number":["2020B0301030007"]}]},{"DOI":"10.13039\/501100018925","name":"111 Center","doi-asserted-by":"crossref","award":["D20008"],"award-info":[{"award-number":["D20008"]}],"id":[{"id":"10.13039\/501100018925","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Double First-class Discipline Promotion Project","award":["2023B10564003"],"award-info":[{"award-number":["2023B10564003"]}]},{"DOI":"10.13039\/501100010226","name":"Department of Education of Guangdong Province","doi-asserted-by":"publisher","award":["2019KZDXM004, 2019KCXTD001"],"award-info":[{"award-number":["2019KZDXM004, 2019KCXTD001"]}],"id":[{"id":"10.13039\/501100010226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Laboratory of Lingnan Modern Agriculture Project","award":["NT2021007"],"award-info":[{"award-number":["NT2021007"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,6,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Sporadic human infections of avian influenza virus (AIV) raise significant public health concerns. A critical factor limiting the transmission of AIVs is the shift in receptor-binding preference from Sia\u03b12,3 to Sia\u03b12,6. To reveal the adaptive selection dynamics during the host adaptation process of AIVs, this study generated a viral library with random mutations in the HA gene of the H9N2 strain. Upon passaging the viral library in chickens and mice, the predominantly selected variants exhibited a preference for Sia\u03b12,3 receptors. Notably, the wild-type strain remained dominant in both inoculated and direct-contact chickens, while variants with the \u0394L226\/R229I substitutions were preferentially selected in mice. Ferrets have a predominance of Sia\u03b12,6 in their respiratory tract. As expected, the variant harboring the N289D mutation, which prefers Sia\u03b12,6 binding, was enriched during\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      passaging in ferrets. The mice-adapted variant with the \u0394L226\/R229I mutations causes reduced levels of TNF-\u03b1 in the early days post-infection in mice, which correlated with an increase in its viral titers. Conversely, elevated levels of IL-6 and IL-1\u03b2 at five dpi may contribute to the development of the cytokine release syndrome, potentially elucidating the higher fatality rate observed. In conclusion, based on the mutant spectra of the HA gene, this study elucidates the distinct quasispecies dynamics during the adaptation of H9N2 to different hosts, with receptor availability serving as one of the driving factors. Furthermore, a series of critical substitutions that influence the interspecific transmission potential of H9N2 AIVs were identified.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>The mutation of viruses creates a quasispecies reservoir. In this study, we aimed to investigate the dynamics of quasispecies during the host adaptation of AIVs. We generated a viral library with random mutations in the HA gene of H9N2 and conducted serial passaging in chickens, mice, and ferrets for five generations, respectively. The wild-type strain was dominant in chickens, while mice selected viruses with the \u0394L226\/R229I substitutions. Both variants showed a preference for binding to Sia\u03b12,3, which aligned with the abundance of Sia\u03b12,3 found in the respiratory tract epithelial cells of chickens and mice. In ferrets, where Sia\u03b12,6 is more prevalent, the variant with the N289D mutation, which prefers Sia\u03b12,6, was found to be enriched. In summary, this study revealed the adaptive selection of H9N2 quasispecies in various hosts, contributing to our understanding of AIV host adaptation.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00151-25","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T09:00:23Z","timestamp":1746694823000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Adaptive selection of quasispecies during\n                    <i>in vivo<\/i>\n                    passaging in chickens, mice, and ferrets results in host-specific strains for the H9N2 avian influenza virus"],"prefix":"10.1128","volume":"99","author":[{"given":"Yiliang","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8114-9782","authenticated-orcid":false,"given":"Xi","family":"Quan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5068-4177","authenticated-orcid":false,"given":"Rujian","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingde","family":"Gan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Irwin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto","place":["Toronto, Canada"]},{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Banting and Best Diabetes Centre, University of Toronto","place":["Toronto, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7660-5522","authenticated-orcid":true,"given":"Yongyi","family":"Shen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05v9jqt67","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Agriculture and Biology, Shanghai Jiao Tong University","place":["Shanghai, China"]},{"name":"Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/v10090497"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44358-024-00008-7"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2022.2155072"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/v11070620"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00414"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12515"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/emi.2017.94"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19671-3"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2019.01.002"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virs.2024.12.010"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178328"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2017.10.026"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12050541"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-013-1888-7"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001005"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-091919-105900"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.12.6278-6281.1990"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008271"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-26397-7_3"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy082"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01328"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/82_2014_423"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00793-6"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00037-06"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2012.03.003"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0115-z"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.11.002"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.602124"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004508"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.78.1.240-249.2004"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.02.015"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.74.18.8502-8512.2000"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2018.06.018"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2008.10.027"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-animal-022114-111017"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.1.129-149.2001"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-43-28"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2024.2373314"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.588541"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2018.1540586"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3362"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.215667"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00867-7"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031721"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052719"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13071362"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2020.603584"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.659419"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01158"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.adg7867"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100133697"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10831"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03110-12"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.201401198"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01379-22"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00151-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00151-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:24:19Z","timestamp":1780590259000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00151-25"}},"subtitle":[],"editor":[{"given":"Colin R.","family":"Parrish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,17]]},"references-count":59,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6,17]]}},"alternative-id":["10.1128\/jvi.00151-25"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00151-25","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,17]]},"assertion":[{"value":"2025-01-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00151-25"}}