OmniVira

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

Hao Song1,2 Jianxun Qi2 Haixia Xiao3,4 Yuhai Bi5,4 Wei Zhang2 Ying Xu5,6 Fei Wang2 Yi Shi5,7,8 George F Gao1,5,3,7,9,10,11
Affiliations 11 institutions
  1. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, 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
  4. 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
  6. School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
  7. Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China
  8. Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
  9. School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China
  10. Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China
  11. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: [email protected].
PMID28768203 DOI10.1016/j.celrep.2017.07.028 Year2017 Journal Cell reports Cell Rep Languageeng Statusppublish

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.

Supporting text Virus Host Location
crystal structure 4 H4 hemagglutinin 1 H4N6 2 host jump 3 influenza virus 29 receptor binding 30 transmission 55 Hemagglutinin Glycoproteins, Influenza Virus 180 Influenza A virus 186 Mutation, Missense 26 Amino Acid Substitution 81 Humans 1440 hemagglutinin, human influenza A virus 5

Evidence records

2 total
Functional Mechanism
2 records · 2 evidence types
Evidence type Receptor Usage
1 records
OVE2669 Receptor Usage
Key finding

The avian H4N6 isolate binds avian receptors whereas the swine H4N6 isolate binds human receptors, showing host-dependent receptor usage.

Virus
Influenza A virus H4N6
Host
birds Aves Experimental system pig Sus scrofa Experimental system human Homo sapiens Experimental system
Location
Not specified
Supporting text

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.

Method
receptor-binding assay | hemagglutinin receptor-binding analysis
Receptors
avian receptors | human receptors
Evidence type Molecular Adaptation
1 records
OVE2670 Molecular Adaptation
Key finding

Q226L and G228S substitutions in influenza A H4N6 hemagglutinin drive a receptor-binding switch from avian to human specificity.

Virus
Influenza A virus H4N6
Host
Not specified
Location
Not specified
Supporting text

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.

Genes or proteins
hemagglutinin
Receptors
avian receptors | human receptors
Mutations
Q226L | G228S
Mechanism types
receptor binding | host-range expansion