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In order to evaluate the epidemiology of influenza A and its surface antigens (haemagglutinin [HA] and neuraminidase [NA]) for molecular epidemiology and evolution analysis during winter 2012–2013 in Beijing, China, we worked within the framework of the Chinese National Influenza Center and collected nasal swabs of patients presenting with influenza-like illness. We found that both A(H1N1)pdm09 (46.8%) and H3N2 (53.2%) viruses were the predominant strains during the 2012–2013 influenza epidemic. The peak phase started at the second week of 2013 and lasted about 1 month. We obtained HA and NA sequences of viruses from 44 patients by using Sanger sequencing. None of the strains had the oseltamivir resistance site H274Y. Phylogenetic analysis of 29 A(H1N1)pdm09 viruses showed a genetic drift from the vaccine strain A/California/07/2009 with mutations (H155Q/R and L178I) at the antigenic sites Ca and Sa of HA; the strains were classified into genetic groups 6 and 7 because of the presence of D114N, S160G, S202T, and A214T mutations in HA. H3N2 viruses formed seasonal phylogenetic clusters representative for each season from 2000 to 2013; 15 of the 2012–2013 H3N2 strains were assigned to the A/Victoria/361/2011 genetic clade with mutations at the antigenic sites A, B and C of HA, including R158K/G, N161S, Q172H, and N294K; the 2012–2013 strains with V239I, S61N, T64I, and A214S HA mutations were classified into subgroup 3C. The mutation of potential N-linked glycosylation residues at the antigenic sites of HA and around the enzymatic active center of NA may have increased viral pathogenicity by masking antigenic sites from immune recognition. Our data suggest that influenza vaccines are generally effective, but still provide suboptimal protection due to antigenic variation. This study increases the understanding of influenza A viruses in humans and is informative for future vaccine strain selection. [ABSTRACT FROM AUTHOR]