Correlating novel variable and conserved motifs in the Hemagglutinin protein with significant biological functions.
BACKGROUND
Variations in the influenza Hemagglutinin protein contributes to antigenic drift resulting in decreased efficiency of seasonal influenza vaccines and escape from host immune response. We performed an in silico study to determine characteristics of novel variable and conserved motifs in the Hemagglutinin protein from previously reported H3N2 strains isolated from Hong Kong from 1968-1999 to predict viral motifs involved in significant biological functions.


RESULTS
14 MEME blocks were generated and comparative analysis of the MEME blocks identified blocks 1, 2, 3 and 7 to correlate with several biological functions. Analysis of the different Hemagglutinin sequences elucidated that the single block 7 has the highest frequency of amino acid substitution and the highest number of co-mutating pairs. MEME 2 showed intermediate variability and MEME 1 was the most conserved. Interestingly, MEME blocks 2 and 7 had the highest incidence of potential post-translational modifications sites including phosphorylation sites, ASN glycosylation motifs and N-myristylation sites. Similarly, these 2 blocks overlap with previously identified antigenic sites and receptor binding sites.


CONCLUSIONS
Our study identifies motifs in the Hemagglutinin protein with different amino acid substitution frequencies over a 31 years period, and derives relevant functional characteristics by correlation of these motifs with potential post-translational modifications sites, antigenic and receptor binding sites.
Gendoo
Deena M A
DM
YJ-Science and Technology Research Center American University in Cairo, Cairo, Egypt. deena_gendoo@yahoo.com
El-Hefnawi
Mahmoud M
MM
Werner
Mark
M
Siam
Rania
R
D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000940:Antigenic Variation; D019295:Computational Biology; D014644:Genetic Variation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D009154:Mutation; D011499:Protein Processing, Post-Translational
D019267:Hemagglutinin Glycoproteins, Influenza Virus