Molecular tracing of Japan-indigenous hepatitis E viruses

1 Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan 2 Department of Medical Sciences, Toshiba General Hospital, Tokyo 140-8522, Japan 3 Department of Hepatology, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan 4 Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo 006-8555, Japan 5 First Department of Internal Medicine, Iwate Medical University, Iwate 020-8505, Japan 6 Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama 350-0495, Japan 7 Department of Internal Medicine, Kokuho Central Hospital, Nara 636-0302, Japan 8 Department of Internal Medicine, Tottori Red Cross Hospital, Tottori 680-8517, Japan 9 Transfusion Section, University of the Ryukyus School of Medicine, Okinawa 903-0215, Japan 10 Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan 11 Department of Gastroenterology, Juntendo University School of Medicine, Urayasu Hospital, Chiba 279-0021, Japan Correspondence Masashi Mizokami mizokami{at}med.nagoya-cu.ac.jp The ancestor(s) of apparently Japan-indigenous strains of Hepatitis E virus (HEV) was probably of foreign origin, but it remains unclear when and from where it made inroads. In this study, 24 genotype 3 and 24 genotype 4 HEV strains recovered in Japan each showed a significant cluster, clearly distinct from those of foreign strains, in the phylogenetic tree constructed from an 821 nt RNA polymerase gene fragment. The evolutionary rate, approximately 0·8 x 10 –3 nucleotide substitutions per site per year, enabled tracing of the demographic history of HEV and suggested that the ancestors of Japan-indigenous HEV had made inroads around 1900, when several kinds of Yorkshire pig were imported from the UK to Japan. Interestingly, the evolutionary growth of genotype 3 in Japan has been slow since the 1920s, whereas genotype 4 has spread rapidly since the 1980s. In conclusion, these data suggest that the indigenization and spread of HEV in Japan were associated with the popularization of eating pork. The GenBank/EMBL/DDBJ accession numbers for the HEV nucleotide sequences reported in this paper are shown in Fig. 1. Supplementary tables are available in JGV Online.