title: Phylogenetic relationships of the HA and NA genes between vaccine and seasonal influenza A(H3N2) strains in Korea.
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.
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Jin Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Ilseob
authors.initials: I
authors.lastname: Lee
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Sehee
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Joon-Yong
authors.initials: JY
authors.lastname: Bae
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Kirim
authors.initials: K
authors.lastname: Yoo
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Cheong
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Noh
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Kyung Wook
authors.initials: KW
authors.lastname: Hong
authors.affiliation: Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.affiliation: Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Vrancken
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Juwon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Misun
authors.initials: M
authors.lastname: Nam
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Soo-Hyeon
authors.initials: SH
authors.lastname: Yun
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Woo In
authors.initials: WI
authors.lastname: Cho
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Woo Joo
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Mee Sook
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Song
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Sun-Ho
authors.initials: SH
authors.lastname: Kee
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Ki-Joon
authors.initials: KJ
authors.lastname: Song
authors.affiliation: Department of Microbiology, the Institute of Viral Diseases, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Man-Seong
authors.initials: MS
authors.lastname: Park
mesh_terms: D000956:Antigens, Viral / Q000235:genetics; D019143:Evolution, Molecular; D006385:Hemagglutination Inhibition Tests; D006388:Hemagglutinins / Q000235:genetics*; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000472:pathogenicity; D007251:Influenza, Human / Q000235:genetics* / Q000821:virology; D009439:Neuraminidase / Q000235:genetics*; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D056910:Republic of Korea; D012621:Seasons
chemical_list: D000956:Antigens, Viral; D006388:Hemagglutinins; D012367:RNA, Viral; D009439:Neuraminidase