Abstract
BackgroundInfluenza A virus encodes for eleven proteins, of which HA, NA, NS1 and PB1-F2 have been implicated in viral pathogenicity and virulence. Thus, in addition to the HA and NA gene segments, monitoring diversity of NS1 and PB1-F2 is also important.Methods55 out of 166 circulating influenza A strains (31 H1N1 and 24 H3N2) were randomly picked during 2007-2009 and NS and PB1-F2 genes were sequenced. Phylogenetic analysis was carried out with reference to the prototype strains, concurrent vaccine strains and other reference strains isolated world wide.ResultsComparative analysis of both nucleotide and deduced amino acid sequences, revealed presence of NS gene with A/PR/8/34(H1N1)-like mutations (H4N, Q21R, A22V, K44R, N53D, C59R, V60A, F103S and M106I) in both RNA-binding and effector domain of NS1 protein, and G63E, the HPAI-H5N1-like mutation in NEP/NS2 of five A/H1N1 strains of 2007 and 2009. NS1 of other A/H1N1 strains clustered with concurrent A/H1N1 vaccine strains. Of 31 A/H1N1 strains, five had PB1-F2 similar to the H3N2 strains; six had non-functional PB1-F2 protein (11 amino acids) similar to the 2009 pandemic H1N1 strains and rest 20 strains had 57 amino acids PB1-F2 protein, similar to concurrent A/H1N1 vaccine strain. Interestingly, three A/H1N1 strains with H3N2-like PB1-F2 protein carried primitive PR8-like NS gene. Full gene sequencing of PB1 gene confirmed presence of H3N2-like PB1 gene in these A/H1N1 strains.ConclusionOverall the study highlights reassortment event involving gene segments other than HA and NA in the co-circulating A/H1N1 and A/H3N2 strains and their importance in complexity of influenza virus genetics. In contrast, NS and PB1-F2 genes of all A/H3N2 eastern India strains were highly conserved and homologous to the concurrent A/H3N2 vaccine strains suggesting that these gene segments of H3N2 viruses are evolutionarily more stable compared to H1N1 viruses.
Highlights
Influenza A virus encodes for eleven proteins, of which HA, NA, NS1 and PB1-F2 have been implicated in viral pathogenicity and virulence
The complete nucleotide sequence of the NS gene and partial sequence of PB1 gene segment encoding full-length PB1-F2 of representative influenza A (H1N1/H3N2) positive samples collected from the out-patient departments (OPDs) of local hospitals were compared with the concurrent influenza A (H1N1/H3N2) strains, circulating worldwide
In contrast to A/H1N1 strains, all A/H3N2 (n = 24) strains analyzed in this study revealed highly conserved NS and PB1-F2 gene, with >98.5% homology to concurrent A/H3N2 strains circulating worldwide
Summary
Influenza A virus encodes for eleven proteins, of which HA, NA, NS1 and PB1-F2 have been implicated in viral pathogenicity and virulence. The genome of IAV consists of eight singlestranded, negative- sense viral RNA segments encoding the subunits of the transcriptase complex (PB1, PB2, PA), interest in understanding genomic diversity of virus encoded genes implicated in pathogenicity of diseases. One such virulence factor is NS1, which is a multifunctional protein of IAV having role in suppression of host immune and apoptotic responses [2,3]. Though based on overexpression studies, PB1-F2 has been shown to cause cell death in some cell types [1,19], induce inflammation by recruitment of inflammatory cells in mice [18] and to bind to PB1 resulting in increased activity of the influenza virus polymerase in vitro [20]
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