Consequences of asymmetric mutational pressure for the dynamic of linear B-cell epitopes repertoire of influenza a virus neuraminidase rearrangement

Abstract

Full-length nucleotide sequences of avian influenza A virus neuraminidase coding region (20,631 sequences) were analyzed and compared with those isolated from viruses infecting human and swine (63,750 sequences). If in fourfold degenerate sites there is asymmetric A-bias that may be more or less asymmetric depending on the type of neuraminidase and the host, than in twofold degenerate sites from third codon positions there is a strong asymmetric U-bias in coding regions of N4, N5, and N8 isolated from viruses infecting birds, as well as in those of N1 and N2 isolated from viruses infecting human, swine, and birds, while in coding regions of N9 isolated from birds, there is surprisingly strong C-bias, and in sequences of N3, N6, and N7 the usage of C is quite close to the level of U. Revealed stabilization of both U and C in twofold degenerate sites is the evidence of frequent changes in mutational pressure direction. Asymmetric mutational pressure was one of the sources of amino acid replacements that resulted in an equal percentage of sites with appeared and disappeared linear B-cell epitopes in N1, N2, N4, and N5 (33.62–35.33% vs. 32.41–36.45%, respectively), and controlled by the immune pressure it resulted in a stronger tendency to disappear for B-cell epitopes of N3, N6, N7, N8, and N9 of avian viruses (8.74–28.77% vs. 28.96–38.89%). The lack of correlation between nucleotide usages in fourfold and twofold degenerate sites for three nucleotides, except U, is a strong evidence of mutational pressure theory.