Sites In Hemagglutinin Protein Research Articles

Identification of mutations at the antigenic and glycosylation sites in hemagglutinin protein of H5N1 strain.

Hemagglutinin (HA) is the principal antigen, present on the viral surface. It is the primary target for neutralizing antibodies. In this paper, we have carried out studies on human hemagglutinin protein from H5N1 strain with homologous hemagglutinin from non-human sources of H5N1 strains. In all strains, part of the antigenic site (128-141) predicted by computer program "Antigenic", corresponds to immunodominant site Sa of H1 subtype. In AAF02304 strain, A156-->S156 mutation lies at the antigenic subsite of site 2 that corresponds to site B in the H3 subtype. In some strains of non-human origins, there are mutations at the antigenic sites. Interestingly, in AAY56367 strain mutation L138-->H138 lies at the receptor binding site, which also overlaps the antigenic site. Therefore, this amino acid substitution may influence both the specificity of receptor recognition and antibody binding. Seven potential glycosylation sites in human HA and in some strains of non-human sources have been predicted by computer program, Scan Prosite. In some strains of HA from non-human sources because of mutation, an additional glycosylation site appeared at the antigenic site. Therefore in these strains the oligosaccharides will mask the surface of HA as well as antigenic site. Hence these strains will not be recognized by host immune system.

Identifying potential immunodominant amino acid positions in hemagglutinin protein of influenza A H3N2 viruses

Current inactivated influenza vaccines can provide protection when vaccine antigens and circulating viruses share a high degree of similarity in hemagglutinin (HA) protein. Five antigenic sites in hemagglutinin protein have been proposed and 20 amino acid (AA) positions in the five antigenic sites have been mapped to bind with mouse monoclonal antibodies. However, the significance of these AA positions in polyclonal response is unclear. This study is to develop bioinformatics models combining ferret antibody cross-reactivity and virus AA sequence data to identify potential immunodominant AA positions in hemagglutinin protein. One hundred thirty-eight pairwise comparisons on antibody cross-reactivity and AA changes among 33 influenza H3N2 viruses were available. AA changes were found in 79 positions and 22 of the 79 positions were identified to be statistically associated with ferret antibody cross-reactivity ( P<0.05). Effects of these 22 positions need to be verified experimentally using virus variants with point mutations.