Investigating the origin and global dispersal history of hepatitis E virus genotype 4 using phylogeographical analysis

Tatsunori Nakano, Kazuaki Takahashi, Masaharu Takahashi, Yoichi Nishigaki, Naoki Watanabe, Satoshi Ishida, Shino Fujimoto, Hideaki Kato, Hiroshi Okano, Yoshiyuki Takei, Minoru Ayada, Eiichi Tomita, Masahiro Arai, Hiroaki Okamoto, Shunji Mishiro

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Background & Aims: 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.

Original languageEnglish
Pages (from-to)31-41
Number of pages11
JournalLiver International
Issue number1
Publication statusPublished - 01-01-2016

All Science Journal Classification (ASJC) codes

  • Hepatology


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