| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
The host range restriction of influenza viruses is partly attributable to receptor specificity : most avian influenza A viruses preferentially bind to the sialic acid-α2, 3-galactose (SAα2, 3Gal) linkage on sialyloligosaccharides, whereas human viruses bind to SAα2, 6Gal. In this study, we found the positive charge of hemeggulutinin(HA) of human H3N2 viruses has been increasing year by year since they emerged in humans in 1968, resulting in the electrostatic interaction with SAα2, 6Gal, whereas there is no surface charge changes of HA proteins of avian H3N2 viruses. We also found some H5N1 viruses isolated from humans possessing mutations : substitution to basic amino acids, recognized SAα2, 6Gal in the charge dependent manner. These results suggested that charge dependent recognition of human-type receptors is one of the mechanism by which influenza viruses adapt to humans. Moreover, computational simulation of the surface charge of HA proteins appears to be available for the understanding of interaction between HA proteins and receptors. Among mutations unique to human isolates, amino acid substitution at position 182 especially increased the replicative ability of H5N1 viruses in normal human bronchus epithelial cells. However, none of H5N1 viruses tested in this study showed efficient transmission in ferret model.
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