Adaptation of avian influenza A (H6N1) virus from avian to human receptor-binding preference.
The receptor-binding specificity of influenza A viruses is a major determinant for the host tropism of the virus, which enables interspecies transmission. In 2013, the first human case of infection with avian influenza A (H6N1) virus was reported in Taiwan. To gather evidence concerning the epidemic potential of H6 subtype viruses, we performed comprehensive analysis of receptor-binding properties of Taiwan-isolated H6 HAs from 1972 to 2013. We propose that the receptor-binding properties of Taiwan-isolated H6 HAs have undergone three major stages: initially avian receptor-binding preference, secondarily obtaining human receptor-binding capacity, and recently human receptor-binding preference, which has been confirmed by receptor-binding assessment of three representative virus isolates. Mutagenesis work revealed that E190V and G228S substitutions are important to acquire the human receptor-binding capacity, and the P186L substitution could reduce the binding to avian receptor. Further structural analysis revealed how the P186L substitution in the receptor-binding site of HA determines the receptor-binding preference change. We conclude that the human-infecting H6N1 evolved into a human receptor preference.
College of Veterinary Medicine China Agricultural University, Beijing, China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences, Beijing, China.
Fei
F
Wang
CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences, Beijing, China Center of Influenza Research and Early-Warning Chinese Academy of Sciences, Beijing, China.
Jianxun
J
Qi
CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences, Beijing, China Center of Influenza Research and Early-Warning Chinese Academy of Sciences, Beijing, China.
Yuhai
Y
Bi
CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences, Beijing, China Center of Influenza Research and Early-Warning Chinese Academy of Sciences, Beijing, China.
Wei
W
Zhang
College of Veterinary Medicine China Agricultural University, Beijing, China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences, Beijing, China.
Min
M
Wang
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science Chinese Academy of Sciences, Beijing, China Aviation General Hospital, Beijing, China.
Baorong
B
Zhang
College of Veterinary Medicine China Agricultural University, Beijing, China.
Ming
M
Wang
College of Veterinary Medicine China Agricultural University, Beijing, China.
Jinhua
J
Liu
CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences, Beijing, China Center of Influenza Research and Early-Warning Chinese Academy of Sciences, Beijing, China.
Jinghua
J
Yan
CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences, Beijing, China Center of Influenza Research and Early-Warning Chinese Academy of Sciences, Beijing, China Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science Chinese Academy of Sciences, Beijing, China.
Yi
Y
Shi
College of Veterinary Medicine China Agricultural University, Beijing, China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences, Beijing, China Center of Influenza Research and Early-Warning Chinese Academy of Sciences, Beijing, China Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science Chinese Academy of Sciences, Beijing, China National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention (China CDC), Beijing, China Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China gaof@im.ac.cn.
George F
GF
Gao
D000220:Adaptation, Biological / Q000235:genetics*; D019943:Amino Acid Substitution; D000818:Animals; D005075:Biological Evolution; D002645:Chickens; D004372:Ducks; D006801:Humans; D009980:Influenza A virus / Q000235:genetics*; D005585:Influenza in Birds / Q000503:physiopathology* / Q000635:transmission; D007251:Influenza, Human / Q000821:virology*; D016296:Mutagenesis; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013624:Taiwan
D011991:Receptors, Virus
H6N1; crystal structure; hemagglutinin; receptor binding