title: Investigating the origin and global dispersal history of hepatitis E virus genotype 4 using phylogeographical analysis.
abstract: OBJECTIVE
  Hepatitis E virus (HEV) genotype 4 has mainly been isolated from sporadic hepatitis cases and swine in Asian countries. We analysed the origin and global dispersal history of genotype 4 using a Bayesian phylogeographical approach.
  
  
  METHODS
  The 412-nucleotide sequences of open reading frame 2 of genotype 4 (47 Japanese, 40 Chinese, 1 Indian, 8 Indonesian, 1 Korean, 1 Taiwanese, 2 Danish and 2 Italian), of which sampling date and location were known, were collected. Evolutionary rate, divergence time, demographic growth and phylogeography were co-estimated in the Bayesian statistical inference framework implemented in the BEAST package to model spatial dispersal on a time-scaled genealogy.
  
  
  RESULTS
  The most probable origin of genotype 4 was Japan and the time of origin was 1909 (95% highest posterior density, 1871-1940). Seven lineages of genotype 4 migrated from Japan to China. The analysis also showed the migration of genotype 4 from Japan or China to India and Indonesia and from China to Indonesia, Taiwan, Korea and a few European countries.
  
  
  CONCLUSIONS
  Swine trade between countries coincided with the migration time and direction of genotype 4 in some cases and was considered the primary cause of dispersal. However, there was no clear cause of dispersal for some cases, for which no records of pig trade were found. Future research should analyse additional nucleotide sequences paired with epidemiological data from various countries to improve our understanding of HEV dispersal.
authors.affiliation: Department of Internal Medicine, Fujita Health University Nanakuri Sanatorium, Mie, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nishigaki
authors.affiliation: Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Internal Medicine, Kuwana West Medical Center, Kuwana, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishida
authors.affiliation: Department of Internal Medicine, Kuwana West Medical Center, Kuwana, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Fujimoto
authors.affiliation: Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Gastroenterology, Suzuka General Hospital, Mie, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okano
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Department of Gastroenterology, Chutoen General Medical Center, Shizuoka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Ayada
authors.affiliation: Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tomita
authors.affiliation: Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Arai
authors.affiliation: Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Mishiro
mesh_terms: D001499:Bayes Theorem; D004279:DNA, Viral / Q000032:analysis; D016751:Hepatitis E / Q000821:virology*; D016752:Hepatitis E virus / Q000235:genetics*; D006801:Humans; D007564:Japan; D010802:Phylogeny; D058974:Phylogeography / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D062211:Spatio-Temporal Analysis
chemical_list: D004279:DNA, Viral
keywords: genotype 4; hepatitis E virus; origin; phylogeographical analysis; swine trade