{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:00:46Z","timestamp":1785474046796,"version":"3.56.0"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health and Medical Research Fund","award":["14131402"],"award-info":[{"award-number":["14131402"]}]},{"name":"Health and Medical Research Fund","award":["T11-705\/14-N"],"award-info":[{"award-number":["T11-705\/14-N"]}]},{"name":"Health and Medical Research Fund","award":["T11-712\/19-N"],"award-info":[{"award-number":["T11-712\/19-N"]}]},{"name":"Health and Medical Research Fund","award":["HHSN272201400006C"],"award-info":[{"award-number":["HHSN272201400006C"]}]},{"name":"Health and Medical Research Fund","award":["75N93021C00016"],"award-info":[{"award-number":["75N93021C00016"]}]},{"name":"Hong Kong Research Grant Council","award":["14131402"],"award-info":[{"award-number":["14131402"]}]},{"name":"Hong Kong Research Grant Council","award":["T11-705\/14-N"],"award-info":[{"award-number":["T11-705\/14-N"]}]},{"name":"Hong Kong Research Grant Council","award":["T11-712\/19-N"],"award-info":[{"award-number":["T11-712\/19-N"]}]},{"name":"Hong Kong Research Grant Council","award":["HHSN272201400006C"],"award-info":[{"award-number":["HHSN272201400006C"]}]},{"name":"Hong Kong Research Grant Council","award":["75N93021C00016"],"award-info":[{"award-number":["75N93021C00016"]}]},{"name":"National Institutes of Health","award":["14131402"],"award-info":[{"award-number":["14131402"]}]},{"name":"National Institutes of Health","award":["T11-705\/14-N"],"award-info":[{"award-number":["T11-705\/14-N"]}]},{"name":"National Institutes of Health","award":["T11-712\/19-N"],"award-info":[{"award-number":["T11-712\/19-N"]}]},{"name":"National Institutes of Health","award":["HHSN272201400006C"],"award-info":[{"award-number":["HHSN272201400006C"]}]},{"name":"National Institutes of Health","award":["75N93021C00016"],"award-info":[{"award-number":["75N93021C00016"]}]},{"name":"Li Ka Shing Foundation","award":["14131402"],"award-info":[{"award-number":["14131402"]}]},{"name":"Li Ka Shing Foundation","award":["T11-705\/14-N"],"award-info":[{"award-number":["T11-705\/14-N"]}]},{"name":"Li Ka Shing Foundation","award":["T11-712\/19-N"],"award-info":[{"award-number":["T11-712\/19-N"]}]},{"name":"Li Ka Shing Foundation","award":["HHSN272201400006C"],"award-info":[{"award-number":["HHSN272201400006C"]}]},{"name":"Li Ka Shing Foundation","award":["75N93021C00016"],"award-info":[{"award-number":["75N93021C00016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The interspecies transmission of avian influenza viruses remains a significant public health concern. H6 viruses have gained attention following the first human infection by a chicken-origin H6N1 virus (A\/Taiwan\/02\/2013, Hu\/13), highlighting their zoonotic potential. To understand the evolutionary trajectory and mammalian adaptation of this Taiwan lineage, we compared two avian isolates (A\/Chicken\/Taiwan\/CF19\/2009, Ck\/09; A\/Chicken\/Taiwan\/2267\/2012, Ck\/12) and Hu\/13 in vitro and in vivo. Hu\/13 exhibited enhanced replication in MDCK cells, producing larger plaques and higher viral titers than Ck\/09 and Ck\/12. In BALB\/c mice, Hu\/13 demonstrated the highest pathogenicity and mortality, followed by Ck\/12, while Ck\/09 induced minimal morbidity. Hu\/13 and Ck\/12 replicated efficiently in respiratory tissues, eliciting robust cytokine responses and severe pulmonary lesions. In ferrets, Hu\/13 showed relatively efficient transmission, infecting all direct physical-contact and two out of three airborne-contact ferrets, whereas Ck\/09 failed to transmit. Histopathology confirmed escalating lung pathology from Ck\/09 to Ck\/12 and Hu\/13. Whole-genome sequencing identified adaptive mutations in Hu\/13 during ferret replication, though no canonical mammalian-adaptive changes (e.g., PB2-E627K or HA-Q226L) were detected. These findings demonstrate progressive mammalian adaptation, replication efficiency, and transmissibility within the Taiwan H6N1 lineage. Enhanced surveillance is crucial to monitor mammalian-adaptive mutations, informing pandemic preparedness and public health strategies.<\/jats:p>","DOI":"10.3390\/v17050733","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:54:28Z","timestamp":1747724068000},"page":"733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Progressive Adaptation of Subtype H6N1 Avian Influenza Virus in Taiwan Enhances Mammalian Infectivity, Pathogenicity, and Transmissibility"],"prefix":"10.3390","volume":"17","author":[{"given":"Zuoyi","family":"Zheng","sequence":"first","affiliation":[{"name":"Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases (Key Laboratory of Ministry of Education), Joint Institute of Virology (Shantou University-The University of Hong Kong), Shantou University Medical College, Shantou University, Shantou 515063, China"},{"name":"State Key Laboratory of Emerging Infectious Diseases (SKLEID), School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases (Key Laboratory of Ministry of Education), Joint Institute of Virology (Shantou University-The University of Hong Kong), Shantou University Medical College, Shantou University, Shantou 515063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases (Key Laboratory of Ministry of Education), Joint Institute of Virology (Shantou University-The University of Hong Kong), Shantou University Medical College, Shantou University, Shantou 515063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Yan","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases (Key Laboratory of Ministry of Education), Joint Institute of Virology (Shantou University-The University of Hong Kong), Shantou University Medical College, Shantou University, Shantou 515063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-4523","authenticated-orcid":false,"given":"Long","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases (Key Laboratory of Ministry of Education), Joint Institute of Virology (Shantou University-The University of Hong Kong), Shantou University Medical College, Shantou University, Shantou 515063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rirong","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases (Key Laboratory of Ministry of Education), Joint Institute of Virology (Shantou University-The University of Hong Kong), Shantou University Medical College, Shantou University, Shantou 515063, China"},{"name":"State Key Laboratory of Emerging Infectious Diseases (SKLEID), School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Emerging Infectious Diseases (SKLEID), School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Emerging Infectious Diseases (SKLEID), School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Guan","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases (Key Laboratory of Ministry of Education), Joint Institute of Virology (Shantou University-The University of Hong Kong), Shantou University Medical College, Shantou University, Shantou 515063, China"},{"name":"State Key Laboratory of Emerging Infectious Diseases (SKLEID), School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2711-0501","authenticated-orcid":false,"given":"Huachen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Joint Laboratory of Emerging Infectious Diseases, Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases (Key Laboratory of Ministry of Education), Joint Institute of Virology (Shantou University-The University of Hong Kong), Shantou University Medical College, Shantou University, Shantou 515063, China"},{"name":"State Key Laboratory of Emerging Infectious Diseases (SKLEID), School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","unstructured":"CDC (2025, April 16). 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