title: Characterization of genome sequences and clinical features of coxsackievirus A6 strains collected in Hyogo, Japan in 1999-2013.
abstract: Coxsackievirus A6 (CV-A6) is an enterovirus, which is known to cause herpangina. However, since 2009 it has frequently been isolated from children with hand, foot, and mouth disease (HFMD). In Japan, CV-A6 has been linked to HFMD outbreaks in 2011 and 2013. In this study, the full-length genome sequencing of CV-A6 strains were analyzed to identify the association with clinical manifestations. Five thousand six hundred and twelve children with suspected enterovirus infection (0-17 years old) between 1999 and 2013 in Hyogo Prefecture, Japan, were enrolled. Enterovirus infection was confirmed with reverse transcriptase-PCR in 753 children (791 samples), 127 of whom (133 samples) were positive for CV-A6 based on the direct sequencing of the VP4 region. The complete genomes of CV-A6 from 22 positive patients with different clinical manifestations were investigated. A phylogenetic analysis divided these 22 strains into two clusters based on the VP1 region; cluster I contained strains collected in 1999-2009 and mostly related to herpangina, and cluster II contained strains collected in 2011-2013 and related to HFMD outbreak. Based on the full-length polyprotein analysis, the amino acid differences between the strains in cluster I and II were 97.7 ± 0.28%. Amino acid differences were detected in 17 positions within the polyprotein. Strains collected in 1999-2009 and those in 2011-2013 were separately clustered by phylogenetic analysis based on 5'UTR and 3Dpol region, as well as VP1 region. In conclusion, HFMD outbreaks by CV-A6 were recently frequent in Japan and the accumulation of genomic change might be associated with the clinical course.
authors.affiliation: Hyogo Prefectural Institute of Public Health and Consumer Sciences, Public Health Science Research Center, Hyogo, Japan.|Center for Infectious Diseases, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ogi
authors.affiliation: Center for Infectious Diseases, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Yoshihiko
authors.identifier: 0000-0002-5177-7480
authors.initials: Y
authors.lastname: Yano
authors.affiliation: Hyogo Prefectural Institute of Public Health and Consumer Sciences, Public Health Science Research Center, Hyogo, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Chikahira
authors.affiliation: Hyogo Prefectural Institute of Public Health and Consumer Sciences, Public Health Science Research Center, Hyogo, Japan.
authors.forename: Denshi
authors.initials: D
authors.lastname: Takai
authors.affiliation: Hyogo Prefectural Institute of Public Health and Consumer Sciences, Public Health Science Research Center, Hyogo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Oshibe
authors.affiliation: National Institute of Infectious Diseases, Infectious Disease Surveillance Center, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arashiro
authors.affiliation: National Institute of Infectious Diseases, Infectious Disease Surveillance Center, Tokyo, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Hanaoka
authors.affiliation: National Institute of Infectious Diseases, Infectious Disease Surveillance Center, Tokyo, Japan.
authors.forename: Tsuguto
authors.initials: T
authors.lastname: Fujimoto
authors.affiliation: Center for Infectious Diseases, Kobe University Graduate School of Medicine, Hyogo, Japan.
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D003384:Coxsackievirus Infections / Q000473:pathology* / Q000821:virology*; D004770:Enterovirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D016679:Genome, Viral; D005838:Genotype; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D017720:Molecular Epidemiology; D010802:Phylogeny; D017422:Sequence Analysis, DNA
keywords: Japan; coxsackievirus A6; hand, foot, and mouth disease