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...