OmniVira

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

Ying Xu1,2 Ruchao Peng2 Wei Zhang2 Jianxun Qi2 Hao Song3 Sheng Liu1,2 Haiyuan Wang4,5 Min Wang2 Haixia Xiao6 Lifeng Fu4,7 Zheng Fan2 Yuhai Bi4,7 Jinghua Yan8,9,10 Yi Shi4,8,9,10 George F Gao1,4,11,12,13,8,9,14
Affiliations 14 institutions
  1. School of Life Sciences, University of Science and Technology of China, Hefei 230026, 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
  5. Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, China.
  6. Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
  7. Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China.
  8. Center for Influenza Research and Early-Warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China
  9. Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China
  10. Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
  11. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China
  12. Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, China
  13. Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China
  14. Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China. Electronic address: [email protected].
PMID31747596 DOI10.1016/j.celrep.2019.10.047 Year2019 Journal Cell reports Cell Rep Languageeng Statusppublish

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.

Supporting text Virus Host Location
H7N9 27 hemagglutinin 31 influenza A virus 227 interspecies transmission 51 receptor-binding property 1 structural basis 1 Animals 1948 Birds 212 Hemagglutinin Glycoproteins, Influenza Virus 180 Hemagglutinins 24 Humans 1440 Influenza A Virus, H7N9 Subtype 87 Influenza in Birds 341 Influenza, Human 286 Orthomyxoviridae Infections 228 Protein Binding 193 Viral Proteins 152

Evidence records

2 total
Functional Mechanism
2 records · 1 evidence types
Evidence type Molecular Adaptation
2 records
OVE3509 Molecular Adaptation
Key finding

A G186V substitution in the H7N9 avian influenza virus hemagglutinin enables human receptor-binding capacity, indicating molecular adaptation toward human hosts.

Virus
Influenza A virus H7N9
Host
Not specified
Location
Not specified
Supporting text

Mutagenesis and structural studies reveal that a G186V substitution is sufficient for H7N9 AIVs to acquire human receptor-binding capacity.

Genes or proteins
hemagglutinin
Receptors
human receptor
Mutations
G186V
Mechanism types
receptor binding | host-range expansion
OVE3510 Molecular Adaptation
Key finding

In H7N9 avian influenza virus HA, the Q226L substitution favors binding to both avian and human receptors when combined with hydrophobic residues A138, V186, and P221, demonstrating an adaptive route for altered receptor binding.

Virus
Influenza A virus H7N9
Host
Not specified
Location
Not specified
Supporting text

A Q226L substitution would favor binding to both avian and human receptors only when paired with A138/V186/P221 hydrophobic residues.

Genes or proteins
hemagglutinin
Receptors
avian receptor | human receptor
Mutations
Q226L | A138 | V186 | P221
Mechanism types
receptor binding | host-range expansion