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Literature detail

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].
PMID 28768203 2017 Cell Rep eng ppublish
PubMed DOI Browse context

Article

Publication summary

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.

crystal structure H4 hemagglutinin H4N6 host jump influenza virus receptor binding transmission Hemagglutinin Glycoproteins, Influenza Virus Influenza A virus Mutation, Missense Amino Acid Substitution Humans hemagglutinin, human influenza A virus

Structured evidence records

Evidence records

3 total
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.90
Key finding

Amino acid changes Q226L and G228S in H4 hemagglutinin enabled an avian influenza A virus to acquire human receptor-binding properties.

Virus
IAV H4N6
Location
Not specified
Supporting text

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
Analysis methods
comparative genomic analysis; structural analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.98
Key finding

Q226L and G228S mutations in H4 hemagglutinin mediate a receptor-binding switch from avian to human receptors, indicating adaptation of H4 influenza A virus toward human hosts.

Virus
IAV H4N6
Host
Not specified
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. 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.

Genes or proteins
hemagglutinin
Receptors
avian receptors; human receptors
Mutations
Q226L; G228S
Mechanism types
receptor_binding; host_range_adaptation
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.97
Key finding

Avian H4N6 hemagglutinin binds avian-type receptors, while swine H4N6 binds human-type receptors due to Q226L and G228S substitutions enabling human receptor-binding similar to H2 and H3 viruses.

Virus
IAV H4N6
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. 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.

Method
receptor-binding assay; sequence comparison; structural analysis
Receptors
avian receptors / human receptors