Abstract
Seasonal influenza is caused by two influenza A subtype (H1N1 and H3N2) and two influenza B lineage (Victoria and Yamagata) viruses. Of these antigenically distinct viruses, the H3N2 virus was consistently detected in substantial proportions in Korea during the 2010/11-2013/14 seasons when compared to the other viruses and appeared responsible for the influenza-like illness rate peak during the first half of the 2011/12 season. To further scrutinize possible causes for this, we investigated the evolutionary and serological relationships between the vaccine and Korean H3N2 strains during the 2011/12 season for the main antigenic determinants of influenza viruses, the hemagglutinin (HA) and neuraminidase (NA) genes. In the 2011/12 season, when the number of H3N2 cases peaked, the majority of the Korean strains did not belong to the HA clade of A/Perth/16/2009 vaccine, and no Korean strains were of this lineage in the NA segment. In a serological assay, post-vaccinated human sera exhibited much reduced hemagglutination inhibition antibody titers against the non-vaccine clade Korean H3N2 strains. Moreover, Korean strains harbored several amino acid differences in the HA antigenic sites and in the NA with respect to vaccine lineages during this season. Of these, the HA antigenic site C residues 45 and 261 and the NA residue 81 appeared to be the signatures of positive selection. In subsequent seasons, when H3N2 cases were lower, the HA and NA genes of vaccine and Korean strains were more phylogenetically related to each other. Combined, our results provide indirect support for using phylogenetic clustering patterns of the HA and possibly also the NA genes in the selection of vaccine viruses and the assessment of vaccine effectiveness.
Highlights
Influenza virus is a RNA virus that belongs to the family Orthomyxoviridae [1]
For the analysis focusing on the HA and NA clustering patterns of H3N2 stains during the 2011/12 season, Korean sequences from the 2011/12 season were obtained from viral isolates (n = 21) of nasopharyngeal clinical samples that were collected in Korea University Medical Center (KUMC) Guro Hospital, or were downloaded from the Korea Influenza Sequence and Epitope Database (KISED; http://influenza.cdc.go.kr/home/w) (n = 154)
In the HA phylogenetic tree (Fig 2A), the KISED sequences of the 2011/12 season separated into three major Korean clades (Korean HA clade I, light green; Korean HA clade II, violet; and Korean HA clade III, orange), and the KUMC HAs contributed to the Korean HA clades II and III
Summary
Influenza virus is a RNA virus that belongs to the family Orthomyxoviridae [1]. Four antigenically different viruses, the H1N1 and H3N2 subtypes of influenza A virus (IAV) and the Victoria and Yamagata lineages of influenza B virus (IBV), cause seasonal epidemics among humans [2, 3]. Which viruses are likely well-suited for use as vaccine strains is announced by the World Health Organization (WHO) in February and September each year for the countries in the Northern and Southern Hemispheres, respectively [9]. These recommendations follow on a comprehensive process of surveillance and serological evaluation of thousands of contemporary virus strains in cooperation with National Influenza Centers of WHO member states and Collaborating Centers [10]. The number of viral isolates of seasonal influenza viruses and clinical manifestations defined in influenza-like illness (ILI) patients [17, 18] indicate that the H3N2 virus had more pronounced impact on influenza epidemiology in Korea during this season
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