Identity of a novel swine hepatitis E virus in Taiwan forming a monophyletic group with Taiwan isolates of human hepatitis E virus

Abstract

Recently, we found that more than 10% of the cases of acute non-A, non-B, non-C hepatitis in Taiwan were caused by a novel strain of hepatitis E virus (HEV). Since none of these patients had a history of travel to areas where HEV is endemic, the source of transmission remains unclear. The recent discovery of a swine HEV in herd pigs in the United States has led us to speculate that HEV may also circulate in herd pigs in Taiwan and may serve as a reservoir for HEV in Taiwan. Of 275 herd pigs obtained from 10 pig farms in Taiwan, 102 (37%) were seropositive for serum anti-HEV immunoglobulin G (IgG). A 185-bp genomic sequence within the ORF-2 of the HEV genome was amplified and cloned from serum samples of an anti-HEV positive pig and subsequently from serum samples of a patient with acute hepatitis E. Sequence comparison revealed that the swine and human isolates of HEV share 97.3% identity. Phylogenetic analyses further showed that the Taiwan swine and human isolates of HEV form a distinct branch divergent from all other known strains of HEV, including the U.S. swine strain. To examine the potential risk of cross-species transmission of swine HEV to humans, the seroprevalences of anti-HEV IgG in 30 swine handlers, 20 pork dealers, and 50 control subjects were assessed and were found to be 26.7, 15, and 8%, respectively (for swine handlers versus controls, P = 0.048). Our findings may help provide an understanding of the modes of HEV transmission and may also raise potential public health concerns for HEV zoonosis.

FIG. 1

Nucleotide sequence alignments of a 185-bp genomic sequence within the ORF-2 region of HEV. Ch.1, Ch.2, Ch.3, CHb, and CXj are five isolates from China (GenBank accession nos., D11092, L25547, L25595, M94177, and L08816, respectively); Pk, Ind532, Np, Br, Ind, MY, Egy, and Chad are the isolates from Pakistan (accession no. M80581), India (accession no. U62621), Nepal (accession no. AF020607), Myanmar (accession no. M73218), India (accession no. X99441), Myanmar (accession no. D10330), Egypt (accession no. AF051351), and Chad (accession no. U62121), respectively; swUS and USP-1 are swine and human isolates, respectively, from the United States (accession nos. AF011921 and AF035437, respectively); swT74 (accession no. AF077004) is the swine isolate from Taiwan; T821 (accession no. AF077005) is the isolate from patient T821 (this report); Mx (accession no. M74506) is an isolate from Mexico. The nucleotide position is relative to the numbering system for the Burmese isolate (40). The nucleotide sequence of isolate Ch.1 is shown on top, and only nucleotide substitutions are indicated (uppercase) for other isolates.

FIG. 2

Phylogenetic tree based on a 185-bp sequence within the ORF-2 region of the HEV genome. The sources of these isolates are described in the text as well as in the legend to Fig. 1. The phylogenetic tree was constructed with the computer software Clustal with the weighted residue weight table (DNAstar) grounded on the sequence divergence. The length of each pair of branches represents the distance between sequence pairs. The scale beneath the tree measures the distance between sequences. Units indicate the number of substitution events.