Hepatitis E virus is responsible for both sporadic and epidemic hepatitis in developing countries. The nonenveloped virus is 27-34 nm in diameter and has been shown to contain a single-strand, positive-sense, polyadenylylated RNA genome of -7.5 kilobases. The nucleotide sequence of the Burma strain of hepatitis E virus has been reported and three open reading frames (ORFs) have been identified. The deduced amino acid sequence from each of these ORFs was used to synthesize overlapping peptides (decamers overlapping at every fourth amino acid) on a solid phase. These peptides were then tested in an ELISA with pooled acute-phase sera from known cases of enterically transmitted non-A, non-B hepatitis collected in the Sudan. Linear B-cell epitopes were identified in all three ORFs. Epitopes were identified throughout the polyprotein encoded by ORF1, but they appeared to be particularly concentrated in the region of the RNA-dependent RNA polymerase. Distinct epitopes were identified in the presumed structural protein encoded by ORF2, and one epitope was identified dose to the carboxyl terminus of the protein encoded by ORF3. These data precisely pinpoint linear B-cell epitopes recognized by antibodies from patients with acute hepatitis E and identify an antibody response directed against the RNA-dependent RNA polymerase.A major form of non-A, non-B hepatitis is the enterically transmitted (ET-NANB) form that is known to frequently occur in developing countries. Outbreaks of ET-NANB hepatitis in Asia (1-3), USSR (4), Costa Rica and Mexico (5), and several African nations (6) have generally been traced to contaminated water (7,8). Males and females appear to be equally affected, and the clinical course is similar to that of classic hepatitis A except for a high mortality rate (10-20%o) in pregnant women (9, 10). There is no evidence of chronic hepatitis following acute ET-NANB hepatitis (11).Virus-like particles with a diameter of 27-34 nm have been recovered from the stools of patients with ET-NANB hepatitis (10-12). The viral agent has been serially transmitted in cynomolgus macaques (13-15), and a partial cDNA clone from the responsible virus was isolated from infected cynomolgus bile (15). The hepatitis E virus (HEV) appears to be distantly related to known positive-strand RNA viruses (16) and has a genome of -7.5 kilobases (kb) that contains three open reading frames (ORFs) encoding viral proteins (17). ORF1, the largest of the three, extends -5 kb from the 5' end. ORF2, the next largest, begins 37 base pairs (bp) downstream of ORF1 and extends "2 kb to the termination codon present 65 bp from the 3'-terminal stretch of adenosine residues. ORF3 partially overlaps ORF1 and ORF2 and contains only 369 bp (17). ORF1 is believed to encode nonstructural proteins including an RNA-dependent RNA polymerase (RDRP) (15, 16) and a helicase-like region believed to promote the unwinding of DNA-RNA duplexes, which are required for genome replication, recombination, repair, and transcription of viral genes (16). ORF2 en...
