Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4

Hao Song; Jianxun Qi; Haixia Xiao; Yuhai Bi; Wei Zhang; Ying Xu; Fei Wang; Yi Shi; George F Gao

doi:10.1016/j.celrep.2017.07.028

Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4

Cell Rep. 2017 Aug 1;20(5):1201-1214. doi: 10.1016/j.celrep.2017.07.028.

Authors

Hao Song¹, Jianxun Qi², Haixia Xiao³, Yuhai Bi⁴, Wei Zhang², Ying Xu⁵, Fei Wang², Yi Shi⁶, George F Gao⁷

Affiliations

¹ Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
² CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
³ 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 (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
⁵ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
⁶ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
⁷ Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, 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 (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: gaof@im.ac.cn.

PMID: 28768203
DOI: 10.1016/j.celrep.2017.07.028

Abstract

Low-pathogenicity avian influenza viruses (LPAIVs) have caused a global concern to public health since the first novel LPAIV H7N9 outbreak occurred. The receptor-binding properties of the viral hemagglutinin are one key factor for efficient transmission and infection in humans. Recent evidence shows that H4 subtype viruses have been widely circulating in domestic poultry and human asymptomatic infections might have occurred. Here, we evaluated the receptor-binding properties of two representative isolates, avian H4N6 (containing Q226 and G228) and swine H4N6 (containing L226 and S228), and found that the avian isolate preferentially binds to avian receptors, whereas the swine isolate preferentially binds to human receptors. The Q226L and G228S substitutions are pivotal for the receptor-binding switch, which resulted in similar human receptor-binding features to the pandemic H2 and H3, implying that H4 has the potential to cause human infections. This early-warning study calls for future extensive surveillance.

Keywords: H4 hemagglutinin; H4N6; crystal structure; host jump; influenza virus; receptor binding; transmission.

Publication types

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

MeSH terms

Amino Acid Substitution
Hemagglutinin Glycoproteins, Influenza Virus* / chemistry
Hemagglutinin Glycoproteins, Influenza Virus* / genetics
Hemagglutinin Glycoproteins, Influenza Virus* / metabolism
Humans
Influenza A virus* / chemistry
Influenza A virus* / genetics
Influenza A virus* / metabolism
Mutation, Missense*

Substances

Hemagglutinin Glycoproteins, Influenza Virus
hemagglutinin, human influenza A virus