Genetic characterization of influenza viruses from influenza-related hospital admissions in the St. Petersburg and Valencia sites of the Global Influenza Hospital Surveillance Network during the 2013/14 influenza season.

Abstract
Background: Continuous surveillance for genetic changes in circulating influenza viruses is needed to guide influenza prevention and control. Objectives: To compare intra-seasonal influenza genetic diversity of hemagglutinin in influenza A strains isolated from influenza hospital admissions collected at two distinct sites during the same season. Study design: Comparative phylogenetic analysis of full-length hemagglutinin genes from 77 isolated influenza A viruses from the St. Petersburg, Russian Federation and Valencia, Spain sites of the Global Influenza Hospital Surveillance Network (GIHSN) during the 2013/14 season. Results: We found significant variability in A(H3N2) and A(H1N1)pdm09 viruses between the two sites, with nucleotide variation at antigenic positions much lower for A(H1N1)pdm09 than for A(H3N2) viruses. For A(H1N1)pdm09, antigenic sites differed by three to four amino acids from the vaccine strain, two of them common to all tested isolates. For A(H3N2) viruses, antigenic sites differed by six to nine amino acids from the vaccine strain, four of them common to all tested isolates. A fifth amino acid substitution in the antigenic sites of A(H3N2) defined a new Glade, 3C.2. For both influenza A subtypes, pairwise amino acid distances between circulating viruses and vaccine strains were significantly higher at antigenic than at non-antigenic sites. Whereas A(H1N1)pdm09 viruses clustered with Glade 6B and 94% of A(H3N2) with Glade 3C.3, at both study sites A(H3N2) Glade 3C.2 viruses emerged towards the end of the season, showing greater pairwise amino acid distances from the vaccine strain compared to the predominant Glade 3C.3. Conclusions: Influenza A antigenic variants differed between St. Petersburg and Valencia, and A(H3N2) Glade 3C.2 viruses were characterized by more amino acid differences from the vaccine strain, especially at the antigenic sites.
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