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

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 Gao^6,7 Jinhua Liu⁸

Affiliations 8 institutions

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.
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
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.
School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
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: [email protected].
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: [email protected].

PMID37669665 DOI10.1016/j.cell.2023.08.011 Year2023 Journal Cell Languageeng Statusppublish

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.

Supporting text Virus Host Location

airborne transmission 3 avian influenza viruses 5 biological properties 1 ferret 8 H3N8 subtype 1 zoonosis 116 Influenza A Virus, H3N8 Subtype 13 Influenza, Human 286 Animals 1948 Chickens 146 Ferrets 79 Humans 1440 Influenza A Virus, H3N2 Subtype 48 Mice 253 Respiratory Aerosols and Droplets 5

Evidence records

4 total

Experimental Infection

3 records · 3 evidence types

Evidence type Pathogenicity Experiment

1 records

OVE7320 Pathogenicity Experiment

Key finding

Human isolates of H3N8 virus showed higher virulence and caused more severe disease in mice and ferrets than chicken isolates in controlled infection experiments.

Virus

Host

Location

Supporting text

Human isolates of H3N8 virus were more virulent and caused severe pathology in mice and ferrets, relative to chicken isolates.

Method: controlled infection | pathological assessment
Experimental system: animal infection model (mice and ferrets)

Evidence type Host Range Experiment

1 records

OVE7319 Host Range Experiment

Key finding

H3N8 avian influenza viruses were able to infect and replicate efficiently in human bronchial epithelial and lung epithelial cell systems.

Virus

Host

Location

Supporting text

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.

Method: in vitro infection assay | virus replication measurement
Sample type: epithelial cells
Experimental system: human epithelial cell-culture infection model

Evidence type Experimental Transmission

1 records

OVE7321 Experimental Transmission

Key finding

Human-isolated H3N8 influenza virus was experimentally transmissible between ferrets via respiratory droplets.

Virus

Host

Location

Supporting text

H3N8 virus isolated from a patient with severe pneumonia was transmissible between ferrets through respiratory droplets.

Method: ferret transmission experiment | respiratory droplet exposure assay
Experimental system: ferret respiratory droplet transmission model

Functional Mechanism

1 records · 1 evidence types

Evidence type Molecular Adaptation

1 records

OVE7323 Molecular Adaptation

Key finding

Human-isolated H3N8 influenza virus acquired the PB2-E627K substitution and human-receptor-binding preference conferring airborne transmission capability.

Virus

Host

Location

Supporting text

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.

Genes or proteins: PB2
Receptors: human receptor
Mutations: PB2-E627K
Mechanism types: receptor binding | host-range expansion | transmission fitness