Host mediated variation and receptor binding specificity of influenza viruses

Abstract

There are at least two possible mechanisms for the host range variation of influenza A viruses. First mechanism is the pressure of the antibody, this results has already reported by us, in 1989(12). In this case, Ser 205 which is located in antigenic site D in the hemagglutinin trimer. When Ser 205 is substituted to Tyr, receptor binding specificity become 2-6 predominant rather than 2-3 predominant. Ser205 is located far away from the receptor binding pocket in the subunit itself, however, very close to the pocket in the next subunit. When the Ser 205 is substituted to bulky amino acid Tyr, The three dimensional structure of the receptor binding pocket in next subunit may be influenced to become 2-6 binding property rather than 2-3 binding(12). Second mechanism is the selective pressure for the appearance of host cell variant with altered receptor binding specificities(8). In this case, amino acid 226 located in receptor binding pocket is clitical for the recognition of 2-6 and 2-3 linkages. Only single amino acid alteration of Leu 226 to Gln made remarkable change of receptor binding specificity 2-6 to 2-3. In this study, we also identified amino acid 155 Thr, 158 Glu, and 228 Ser of the hemagglutinin which may be clitical for the recognition of the molecular species of sialic acid, such as Neu5Ac and Neu5Gc (11,15,16). Very recently, we reported the amino acid residues contributing to the substrate specificity of the influenza A virus sialidase (13, 14). If these amino acid alteration occurres in the host animal bodies in nature, the virus aquires the new receptor binding specificity which allows the infection to the different animal species, such as bird to human population. This process may be one of the important mechanism for the host mediated variation, and the influenza virus transmission between different hosts, and also emerging of new subtypes of influenza viruses in human population.