title: Tropism and innate host responses of influenza A/H5N6 virus: an analysis ofex vivoandin vitrocultures of the human respiratory tract.
abstract: Since their first isolation in 2013, influenza A/H5N6 viruses have spread amongst poultry across multiple provinces in China and to Laos, Vietnam and Myanmar. So far, there have been 14 human H5N6 infections with 10 fatalities.We investigated the tropism, replication competence and cytokine induction of one human and two avian H5N6 isolates inex vivoandin vitrocultures derived from the human respiratory tract. Virus tropism and replication were studied inex vivocultures of human nasopharynx, bronchus and lung. Induction of cytokines and chemokines was measuredin vitroin virus-infected primary human alveolar epithelial cells.Human H5N6 virus replicated more efficiently than highly pathogenic avian influenza (HPAI) H5N1 virus and as efficiently as H1N1pdm inex vivohuman bronchus and lung and was also able to replicate inex vivocultures of human nasopharynx. Avian H5N6 viruses replicated less efficiently than H1N1pdm in human bronchial tissues and to similar titres as HPAI H5N1 in the lung. While the human H5N6 virus had affinity for avian-like receptors, the two avian isolates had binding affinity for both avian- and human-like receptors. All three H5N6 viruses were less potent inducers of pro-inflammatory cytokines compared with H5N1 virus.Human H5N6 virus appears better adapted to infect the human airways than H5N1 virus and may pose a significant public health threat.
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|These authors contributed equally to the study.
authors.forename: Kenrie P Y
authors.initials: KP
authors.lastname: Hui
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|These authors contributed equally to the study.
authors.forename: Louisa L Y
authors.initials: LL
authors.lastname: Chan
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Denise I T
authors.initials: DI
authors.lastname: Kuok
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|The HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Chris K P
authors.initials: CK
authors.lastname: Mok
authors.affiliation: State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Zi-Feng
authors.initials: ZF
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Run-Feng
authors.initials: RF
authors.lastname: Li
authors.affiliation: Agriculture, Fisheries and Conservation Department, The Government of Hong Kong SAR, Hong Kong SAR, China.
authors.forename: Geraldine S M
authors.initials: GS
authors.lastname: Luk
authors.affiliation: Agriculture, Fisheries and Conservation Department, The Government of Hong Kong SAR, Hong Kong SAR, China.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Lee
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|The HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Jimmy C C
authors.initials: JC
authors.lastname: Lai
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Yen
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Huachen
authors.initials: H
authors.lastname: Zhu
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Pathology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: J S Malik
authors.initials: JS
authors.lastname: Peiris
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China mchan@hku.hk.
authors.forename: Michael C W
authors.initials: MC
authors.lastname: Chan
mesh_terms: D056809:Alveolar Epithelial Cells / Q000821:virology; D000818:Animals; D001717:Birds; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000472:pathogenicity / Q000502:physiology*; D005585:Influenza in Birds / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012137:Respiratory System / Q000473:pathology / Q000821:virology*; D046509:Tissue Culture Techniques; D056189:Viral Tropism; D014779:Virus Replication
chemical_list: D018925:Chemokines; D016207:Cytokines