{"doi":"10.3390/v17050733","title":"Progressive Adaptation of Subtype H6N1 Avian Influenza Virus in Taiwan Enhances Mammalian Infectivity, Pathogenicity, and Transmissibility","abstract":"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.","journal":"Viruses","year":2025,"id":566393,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1457436,"name":"Xifeng Chen","orcid":"0000-0002-2869-9883","position":1,"is_corresponding":false},{"id":1457736,"name":"Rutian Zheng","orcid":null,"position":2,"is_corresponding":false},{"id":1429155,"name":"Zhigang Yan","orcid":null,"position":3,"is_corresponding":false},{"id":1428775,"name":"Long Li","orcid":"0000-0003-1670-4523","position":4,"is_corresponding":false},{"id":1048379,"name":"Rirong Chen","orcid":"0000-0002-3257-2180","position":5,"is_corresponding":false},{"id":475228,"name":"Lifeng Li","orcid":"0000-0002-7492-4017","position":6,"is_corresponding":false},{"id":1291688,"name":"Yongmei Liu","orcid":"0000-0002-7264-7749","position":7,"is_corresponding":false},{"id":104820,"name":"Yi Guan","orcid":"0000-0001-6057-9243","position":8,"is_corresponding":false},{"id":104800,"name":"Huachen Zhu","orcid":"0000-0003-2711-0501","position":9,"is_corresponding":false},{"id":1049064,"name":"Zuoyi Zheng","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:56:36.440192Z","pmid":"40431744","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}