The complete sequence of hepatitis E virus genotype 4 reveals an alternative strategy for translation of open reading frames 2 and 3

Abstract

Isolates of hepatitis E virus (HEV) have recently been described from China that are distinct from Burmese, Mexican and US viruses and constitute a novel genotype (genotype 4). Here, the complete genomic sequence of a representative isolate of genotype 4 HEV, amplified directly from the stool of an acutely infected patient, is presented. Analysis of the entire sequence confirms our previous conclusion, based upon partial sequence data, that these Chinese isolates belong to a novel genotype. Typical of genetic variation in HEV, most nucleotide substitutions occur in the third base of the codon and do not affect the amino acid sequence. The genotype 4 virus is unusual in that a single nucleotide insertion in the ORF 3 region changes the initiation of ORF 3, and perhaps also ORF 2. The consequences of these changes are discussed.

Molecular characterization of swine hepatitis E virus from Southeastern Brazil

“…Genotype 3 groups sequences of isolates found in the Unites States, European countries, Japan and Argentina (10,30,(32)(33)(34)37). Genotype 4 contains sequences of isolates found in China, Taiwan and Japan (15,39,47,48).…”

The Leu477 and Leu613 of ORF2-Encoded Protein Are Critical in Forming Neutralization Antigenic Epitope of Hepatitis E Virus Genotype 4

“…The antibodies elicited from pB166 could neutralize HEV strains of genotypes 1, 2 and 3 (29). HEV genotype 4 is newly identified in China and different from other genotypes in that its ORF2 product is 12 aa longer than that of other HEV isolates due to a single nucleotide insertion in the ORF2 region (19). The neutralization epitope(s) of HEV genotype 4 has not been localized.…”

“…In addition, the recently identified HEV genotype 4 strains are unusual in that a single nucleotide insertion in sequence of ORF2 (19). Accordingly, the pORF2 is 672 aa in length and is 12 aa longer than that of HEV isolates of other three genotypes.…”

“…The virus genome contains three overlapping open reading frames (ORFs), the ORF2 encodes pORF2, a putative capsid protein of 660 aa. Four distinct genotypes of HEV, represented by the Burma strain (genotype 1), Mexico strain (genotype 2), US-1 strain (genotype 3), and the new Chinese variant T1 strain (genotype 4), have been identified in the world according to phylogenetic analysis of the full-length sequences (19). More HEV genotypes and subtypes have been found by analyzing sequences derived from small PCR fragments (20).…”

Serological Evidence for Hepatitis E Virus Infection in Laboratory Monkeys and Pigs in Animal Facilities in Japan

“…By phylogenetic analysis, at least four major genotypes of HEV have been identified [25]. Genotype 1 (G1) HEV was isolated in Asia and Africa [22,11], genotype 2 (G2) in Mexico [34], and genotypes 3 (G3) and 4 (G4) in the United States, European countries, China, Japan, and Vietnam [7,20,24,[27][28][29]35]. These viruses are thought to comprise a single serotype [22].…”