Wei Hu

Abstract: Hemagglutinin (HA) of influenza viruses is a cylindrically shaped homotrimer, where each monomer comprises two disulfide-linked subdomains HA1 and HA2. Influenza infection is initiated by binding of HA1 to its host cell receptors and followed by the fusion between viral and host endosomal membranes mediated by HA2. Human influenza viruses preferentially bind to sialic acid that is linked to galactose by an α2,6-linkage (α2,6), whereas avian and swine influenza viruses preferentially recognize α2,3 or α 2,3/α2,6. For animal influenza viruses to cross host species barriers, their HA proteins must acquire mutations to gain the capacity to allow human-to-human transmission. In this study, the informational spectrum method (ISM), a bioinformatics approach, was applied to identify mutations and to elucidate the contribution to the receptor binding specificity from each mutation in HA1 in various subtypes within or between hosts, including 2009 human H1N1, avian H5N1, human H5N1, avian H1N1, and swine H1N2. Among others, our quantitative analysis indicated that the mutations in HA1 of 2009 human H1N1 collectively tended to reduce the swine binding affinity in the seasonal H1N1 strains and to increase that in the pandemic H1N1 strains. At the same time, they increased the human binding affinity in the pandemic H1N1 strains and had little impact on that in the seasonal H1N1 strains. The mutations between the consensus HA1 sequences of human H5N1 and avian H5N1 increased the avian binding affinity and decreased the human binding affinity in avian H5N1 while produced the opposite effects on those in human H5N1. Finally, the ISM was employed to analyze and verify several mutations in HA1 well known for their critical roles in binding specificity switch, including E190D/G225D in H1N1 and Q192R/ S223L/ Q226L/ G228S in H5N1.

Keywords: Binding Specificity; Discrete Fourier Transform; Electron-Ion Interaction Potential; Entropy; Hemagglutinin; Influenza; Informational; Spectrum Method; Mutation; Receptor

Cite this paper: nullHu, W. (2010) Quantifying the effects of mutations on receptor binding specificity of influenza viruses. Journal of Biomedical Science and Engineering, 3, 227-240. doi: 10.4236/jbise.2010.33031.

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