Avian-to-Human Receptor-Binding Adaptation of Avian H7N9 Influenza Virus Hemagglutinin

Ying Xu; Ruchao Peng; Wei Zhang; Jianxun Qi; Hao Song; Sheng Liu; Haiyuan Wang; Min Wang; Haixia Xiao; Lifeng Fu; Zheng Fan; Yuhai Bi; Jinghua Yan; Yi Shi; George F Gao

doi:10.1016/j.celrep.2019.10.047

Avian-to-Human Receptor-Binding Adaptation of Avian H7N9 Influenza Virus Hemagglutinin

Cell Rep. 2019 Nov 19;29(8):2217-2228.e5. doi: 10.1016/j.celrep.2019.10.047.

Authors

Ying Xu¹, Ruchao Peng², Wei Zhang², Jianxun Qi², Hao Song³, Sheng Liu¹, Haiyuan Wang⁴, Min Wang², Haixia Xiao⁵, Lifeng Fu⁶, Zheng Fan², Yuhai Bi⁶, Jinghua Yan⁷, Yi Shi⁸, George F Gao⁹

Affiliations

¹ School of Life Sciences, University of Science and Technology of China, Hefei 230026, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
² CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
³ Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China; Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, China.
⁵ Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
⁶ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China; Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China.
⁷ Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
⁸ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China; Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
⁹ School of Life Sciences, University of Science and Technology of China, Hefei 230026, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China; Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, China; Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China; Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China. Electronic address: [email protected].

PMID: 31747596
DOI: 10.1016/j.celrep.2019.10.047

Abstract

Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,600 human infections, posing a threat to public health. An emerging concern is whether H7N9 AIVs will cause pandemics among humans. Molecular analysis of hemagglutinin (HA), which is a critical determinant of interspecies transmission, shows that the current H7N9 AIVs are still dual-receptor tropic, indicating limited human-to-human transmission potency. Mutagenesis and structural studies reveal that a G186V substitution is sufficient for H7N9 AIVs to acquire human receptor-binding capacity, and a Q226L substitution would favor binding to both avian and human receptors only when paired with A138/V186/P221 hydrophobic residues. These data suggest a different evolutionary route of H7N9 viruses compared to other AIV-subtype HAs.

Keywords: H7N9; hemagglutinin; influenza A virus; interspecies transmission; receptor-binding property; structural basis.

Publication types

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

MeSH terms

Animals
Birds
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Hemagglutinin Glycoproteins, Influenza Virus / metabolism*
Hemagglutinins / genetics
Hemagglutinins / metabolism*
Humans
Influenza A Virus, H7N9 Subtype / genetics
Influenza A Virus, H7N9 Subtype / pathogenicity*
Influenza in Birds / virology
Influenza, Human / metabolism
Influenza, Human / virology*
Orthomyxoviridae Infections / genetics
Orthomyxoviridae Infections / pathology
Protein Binding / genetics
Protein Binding / physiology
Viral Proteins / genetics
Viral Proteins / metabolism

Substances

Hemagglutinin Glycoproteins, Influenza Virus
Hemagglutinins
Viral Proteins