Genetic ancestor of external antigens of pandemic influenza A/H1N1 virus.

Environmental Nanotechnology Division, Sri Paramakalyani Centre for Environmental Sciences, Manonmaniam Sundaranar University, Alwarkurichi, 627412, Tamilnadu, India.
Interdisciplinary Sciences Computational Life Sciences (Impact Factor: 0.67). 12/2012; 4(4):282-90. DOI: 10.1007/s12539-012-0136-7
Source: PubMed

ABSTRACT The aim of the present investigation was to discover the genetic relationships of 2009 pandemic novel influenza A/H1N1 virus (NIV) external antigens Hemagglutinin (HA) and Neuraminidase (NA) with other influenza viruses by performing phylogenetic, comparative and statistical analyses. Phylogenetic trees of these two antigens show that the sequences of the NIV viruses are relatively homogeneous and these were derived from several viruses circulating in swine. The phylogenetic tree of HA shows that NIV had the closest relationship with North-American pig lineages whereas NA had with European pig lineages. In both segments, NIVs had the closest genetic relationship with swine influenza virus lineages. It strongly suggests that pigs are the most possible animal reservoir. Comparative analysis shows that among clade A, NIVs had very low genetic divergence as well as high similarity and also suffered strong purifying selection whereas neighbor clade B shows moderate values when compared to those of clades C-F. It indicates that classical swine influenza viruses present in clade B might be an ancestor of NIVs external antigens. The process of re-assortment occurred in classical swine influenza viruses. The mutation sites exclusively fixed in the NIV of swine and human along with vaccine strain provide an important suggestion for disease diagnosis and vaccine research.

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    ABSTRACT: In the twenty-first century, the first pandemic novel human influenza A/H1N1virus (NIV) outbreak was reported at Mexico and USA on March and early April, 2009 respectively. The outbreak occurred among human populations due to the presence of meager or no immune response against newly emerged viruses. The success of vaccines and drugs depends on their low susceptibility to the formation of escape mutants in virus. Identification of excess, non-synonymous substitutions over synonymous ones is a main indicator of positive Darwinian selection in protein-coding genes of NIVs. The positive Darwinian selection operating on each site of proteins were inferred by computing ω, the ratio of the non-synonymous/synonymous substitutions [dN/dS (or) Ka/Ks], which was calculated by three different methods in terms of codon-based maximum likelihood, branch-site and empirical Bayesian methods under various models. Totally, nine sites from PB2, PB1, HA, M2 and NS1 are inferred as positively selected. The function for amino acid sites of NIVs proteins under positive selection are inferred by comparing the sites with experimentally determined functionally known amino acid sites. Completely 4 positively selected sites of PB1, HA and M2 are found to be involved in B-cell epitopes (BCEs). Interestingly, most of these sites are also involving in T-cell epitopes (TCEs). However, more sites under positive selection forces are involved in TCEs than those of BCEs. Amino acid sites engaged in both BCEs and TCEs should be measured as highly suitable targets, because these sites could induce the strong humoral and cellular immune responses against targets.
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