title: Identification of amino acids in highly pathogenic avian influenza H5N1 virus hemagglutinin that determine avian influenza species specificity.
abstract: To test the role of neutralizing antibodies (nAbs) and receptor adaptation in interspecies transmission of influenza virus, two H5N1 strains, isolated from human and avian hosts, with four amino acid differences in hemagglutinin (HA) and seven HA mutations were studied. We found that a mutation at amino acid position 90 in the H5N1 HA, outside the receptor-binding domain (RBD), could simultaneously induce changes in the RBD conformation to escape from nAb binding and alter the receptor preference through long-range regulation. This mutation was deemed a "key event" for interspecies transmission. It is likely a result of positive selection caused by antibodies, allowing the original invasion by new species-specific variants. A mutation at amino acid position 160 in the RBD only induced a change in receptor preference. This mutation was deemed a "maintaining adaptation", which ensured that influenza virus variants would be able to infect new organisms of a different species successfully. The mutation is the result of adaptation caused by the receptor. Our results suggest that continuing occurrence of these two types of mutations made the variants persist in the new host species.
authors: The Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
authors: Zheng
authors: Z
authors: Li
authors: Zhonghua
authors: Z
authors: Liu
authors: Chi
authors: C
authors: Ma
authors: Linqi
authors: L
authors: Zhang
authors: Yuelong
authors: Y
authors: Su
authors: George F
authors: GF
authors: Gao
authors: Zi
authors: Z
authors: Li
authors: Lianxian
authors: L
authors: Cui
authors: Wei
authors: W
authors: He
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001717:Birds; D002460:Cell Line; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D058507:Host Specificity; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D005585:Influenza in Birds / Q000276:immunology / Q000821:virology*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary
chemical_list: D000914:Antibodies, Viral; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus