Airborne transmission of human-isolated avian H3N8 influenza virus between ferrets

Honglei Sun; Han Li; Qi Tong; Qiqi Han; Jiyu Liu; Haili Yu; Hao Song; Jianxun Qi; Jiaqi Li; Jizhe Yang; Riguo Lan; Guojing Deng; Haoyu Chang; Yajin Qu; Juan Pu; Yipeng Sun; Yu Lan; Dayan Wang; Yi Shi; William J Liu; Kin-Chow Chang; George F Gao; Jinhua Liu

doi:10.1016/j.cell.2023.08.011

Airborne transmission of human-isolated avian H3N8 influenza virus between ferrets

Cell. 2023 Sep 14;186(19):4074-4084.e11. doi: 10.1016/j.cell.2023.08.011. Epub 2023 Sep 4.

Authors

Honglei Sun¹, Han Li¹, Qi Tong¹, Qiqi Han¹, Jiyu Liu¹, Haili Yu¹, Hao Song², Jianxun Qi³, Jiaqi Li¹, Jizhe Yang¹, Riguo Lan¹, Guojing Deng¹, Haoyu Chang¹, Yajin Qu¹, Juan Pu¹, Yipeng Sun¹, Yu Lan⁴, Dayan Wang⁴, Yi Shi³, William J Liu⁴, Kin-Chow Chang⁵, George F Gao⁶, Jinhua Liu⁷

Affiliations

¹ National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
² Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
³ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
⁴ Chinese National Influenza Center (CNIC), NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
⁵ School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
⁶ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Chinese National Influenza Center (CNIC), NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: gaof@im.ac.cn.
⁷ National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address: ljh@cau.edu.cn.

PMID: 37669665
DOI: 10.1016/j.cell.2023.08.011

Abstract

H3N8 avian influenza viruses (AIVs) in China caused two confirmed human infections in 2022, followed by a fatal case reported in 2023. H3N8 viruses are widespread in chicken flocks; however, the zoonotic features of H3N8 viruses are poorly understood. Here, we demonstrate that H3N8 viruses were able to infect and replicate efficiently in organotypic normal human bronchial epithelial (NHBE) cells and lung epithelial (Calu-3) cells. Human isolates of H3N8 virus were more virulent and caused severe pathology in mice and ferrets, relative to chicken isolates. Importantly, H3N8 virus isolated from a patient with severe pneumonia was transmissible between ferrets through respiratory droplets; it had acquired human-receptor-binding preference and amino acid substitution PB2-E627K necessary for airborne transmission. Human populations, even when vaccinated against human H3N2 virus, appear immunologically naive to emerging mammalian-adapted H3N8 AIVs and could be vulnerable to infection at epidemic or pandemic proportion.

Keywords: H3N8 subtype; airborne transmission; avian influenza viruses; biological properties; ferret; zoonosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chickens
Ferrets
Humans
Influenza A Virus, H3N2 Subtype
Influenza A Virus, H3N8 Subtype*
Influenza, Human*
Mice
Respiratory Aerosols and Droplets