In silico characterization of the functional and structural modules of the hemagglutinin protein from the swine-origin influenza virus A (H1N1)-2009.
The 2009 swine-origin influenza virus (S-OIV, H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health Organization. In order to uncover clues about the determinants for virulence and pathogenicity of the virus, we characterized the functional modules of the surface glycoprotein hemagglutinin (HA), the most important protein in molecular epidemiology and pathogenesis of influenza viruses. We analyzed receptor binding sites, basic patch, neutralization antibody epitopes and T cell epitopes in the HA protein of the current S-OIV according to the corresponding functional and structural modules previously characterized in other H1 HA molecules or HA molecules of other subtypes. We compared their differences and similarities systematically. Based on the amino acids defined as the functional and structural modules, the HA protein of 2009 S-OIV should specifically bind to the human 2,6-receptor. The D225G/E mutation in HA, which is found in some isolates, may confer dual binding specificity to the 2,3- and 2,6-receptor based on previously reported work. This HA variant contains two basic patches, one of which results in increased basicity, suggesting enhanced membrane fusion function. The 2009 S-OIV HA also has an extra glycosylation site at position 276. Four of the five antibody neutralization epitopes identified in A/RP/8/34(H1N1) were exposed, but the other was hidden by a glycosylation site. The previously identified cytotoxic T cell epitopes in various HA molecules were summarized and their corresponding sequences in 2009 S-OIV HA were defined. These results are critical for understanding the pathogenicity of the virus and host immune response against the virus.
Sun
YePing
Y
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
Shi
Yi
Y
Zhang
Wei
W
Li
Qing
Q
Liu
Di
D
Vavricka
Christopher
C
Yan
JingHua
J
Gao
George F
GF
D000595:Amino Acid Sequence; D001665:Binding Sites; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D011991:Receptors, Virus / Q000378:metabolism
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus