Japanese patients with sporadic acute hepatitis E are infected with polyphyletic strains of hepatitis E virus (HEV). Hepatitis E is considered a zoonotic disease. Thus far in Japan, only three strains of swine HEV have been identified and an antibody study for HEV antibodies has not been done on Japanese pigs. To determine the prevalence of swine HEV infection in Japan and the extent of genetic variation among Japanese swine HEV strains, we tested serum samples obtained from 2500 pigs from 2 to 6 months of age at 25 commercial swine farms in Japan for the presence of IgG antibodies to HEV and swine HEV RNA. Anti-HEV antibodies were detected in 1448 pigs (58 %). One-hundred-and-thirteen (15 %) of the 750 3-month-old pigs and 24 (13 %) of the 180 4-monthold pigs were positive for swine HEV RNA. The nucleotide sequence of a 412 bp region within open reading frame 2 of the 137 swine HEV isolates was determined. Sequence analyses revealed that the 137 isolates shared 76?6-100 % nucleotide sequence identities and were classifiable into genotype III (93 %) or IV (7 %) and that the isolates from the same farm were ¢97?1 % similar to each other. Phylogenetic analysis showed that the Japanese swine and human HEV isolates segregated into four clusters, with the highest nucleotide identity being 94?4-100 % between swine and human isolates in each cluster. These results indicate that swine HEV is widespread in the Japanese swine population and further support the hypothesis that swine serve as reservoirs for HEV infection. INTRODUCTIONHepatitis E virus (HEV) is an unclassified virus that is the major causative pathogen of enterically transmitted non-A, non-B hepatitis in many developing countries in Asia, Africa and Latin America (Purcell & Emerson, 2001a). There is a growing consensus that HEV-associated hepatitis also occurs among individuals in industrialized nations who have no history of travel to areas endemic for HEV (Harrison, 1999;Purcell & Emerson, 2001a;Schlauder & Mushahwar, 2001).The genome of HEV is a single-stranded, positive-sense RNA of approximately 7?2 kb and contains a short 59 untranslated region (59UTR), three open reading frames (ORF1, ORF2 and ORF3) and a short 39UTR terminated by a poly(A) tract (Reyes et al., 1990;Tam et al., 1991). HEV sequences have tentatively been classified into four major genetic groups (genotypes I-IV) (Schlauder & Mushahwar, 2001). The majority of HEV infections in several countries in Asia and Africa are caused by genotype I and the majority of HEV infections in Mexico and Nigeria are caused by genotype II, while only isolated cases of infection with HEV of genotype III or IV have been described in the US, European countries, Argentina, Taiwan and China (Hsieh et al., 1999;Pina et al., 2000;Schlauder et al., 1998Schlauder et al., , 1999Schlauder et al., , 2000Wang et al., 1999Wang et al., , 2000Wang et al., , 2001Worm et al., 2000;Zanetti et al., 1999). In Japan, 13 % (11/87) of the cases of acute non-A, non-B, non-C hepatitis were caused by HEV infection (Mizuo et al., 20...

The full-length genomic sequences were determined of Japanese swine and human hepatitis E virus (HEV) isolates (swJ13-1 and HE-JA1, respectively) with 100 % identity in the partial sequence of open reading frame (ORF) 2 (ORF2, 412 nt). swJ13-1 was isolated from a 4-month-old farm pig born in Hokkaido, Japan, in 2002 and HE-JA1 was recovered from a 55-year-old patient who lived in Hokkaido and who had contracted sporadic acute hepatitis E in 1997. Both isolates consisted of 7240 nt, excluding the poly(A) tail, and contained three ORFs (ORFs 1-3) that encoded proteins of 1707, 674 and 114 aa. The overall nucleotide sequence identity between them was 99?0 % and the deduced amino acid sequence identities of ORFs 1-3 were 99?8, 100 and 100 %, respectively. The high degree of genomic similarity observed between swine and human HEV isolates in a restricted area of Japan further supports the finding that sporadic hepatitis E in Japan is a zoonosis.Hepatitis E virus (HEV), the causative agent of hepatitis E, is a single-stranded, positive-sense, naked RNA virus (Purcell & Emerson, 2001a). Hepatitis E is an important public concern in many developing countries in Asia, Africa and Latin America, wherein both epidemic and sporadic forms exist (Purcell & Emerson, 2001a). Recent studies have documented that HEV-associated hepatitis also occurs among individuals in industrialized countries with no history of travel to areas endemic for HEV (Harrison, 1999;Purcell & Emerson, 2001a;Schlauder & Mushahwar, 2001;Smith, 2001) and that HEV is a potential zoonotic virus, as suggested by the close genetic relationship between human and swine viruses (Erker et al., 1999; Hsieh et al., 1999;Meng et al., 1997;Pina et al., 2000;Wu et al., 2002) and experimental cross-species infection of swine HEV to a chimpanzee and rhesus monkeys (Meng et al., 1998). The genome of HEV is approximately 7?2 kb long and contains a short 59 untranslated region (UTR), three open reading frames (ORFs 1-3) and a short 39 UTR terminated by a poly(A) tract (Reyes et al., 1990;Tam et al., 1991). Based on sequence analyses, the HEV isolates identified worldwide have been classified tentatively into four major genotypes (Schlauder & Mushahwar, 2001). These include genotypes I (HEV isolates from several countries in Asia and Africa), II (HEV isolates from Mexico and Nigeria), III (HEV isolates from the United States, European countries and Argentina) and IV (HEV isolates from China and Taiwan) (Hsieh et al., 1999;Pina et al., 2000;Schlauder et al., 1998Schlauder et al., , 1999Schlauder et al., , 2000Wang et al., 1999Wang et al., , 2000Wang et al., , 2001aWorm et al., 2000;Zanetti et al., 1999). In Japan, multiple HEV strains of genotype III or IV have been isolated from patients with sporadic acute or fulminant hepatitis of non-A, non-B, non-C aetiology who had not travelled abroad Mizuo et al., 2002;Suzuki et al., 2002;Takahashi et al., 2001Takahashi et al., , 2002a and from farm pigs (Okamoto et al., 2001;Takahashi et al., 2003). In our previous study, we identifie...

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