The Epidemiology of Hepatitis E Virus Infection in Israel and Potential Risk Factors, a Multicenter, Comparative, Cross-sectional Study

Hepatitis E virus is a single-stranded positive-sense RNA virus with genome of approximately 7.2kb in length. The HEV genome is capped at the 5' end followed by a small untranslated region of 27 nucleotides and polyadenalated at the 3' end preceded by another UTR of 65 nucleotides . HEV has three open reading frames: ORF1, ORF2 and ORF3 that encode structural and non- structural proteins. ORF1 is the largest one, approximately 5,000 nt in length, located at the 5 ' end and encodes important proteins for the replication process (methyltransferase, papain-like cysteine protease, helicase, and RNA-dependent RNA polymerase). A noncoding, hypervariable region within ORF1 displays substantial genetic diversity; this region seems to modulate the efficiency of HEV replication. Notably, the differences in the genome size among different HEV strains are confined mainly to this region .ORF2 is located at the 3' end, encodes structural capsid proteins of 660 amino acids and contains three potential glycosylation sites. The ORF2 protein contains multiple immunogenic sites and neutralizing antibodies are directed against it al., .The essential region in the protein for immunogenicity is 452aa-617aa and the neutralizing epitopes have recently been shown to be conformational .ORF3 is located between the other two reading frames and encodes a small phosphoprotein of 123 amino acids. Its exact function has not been yet determined, however, multiple functions have been proposed. It is thought to interact with cellular mitogen-activated protein kinase phosphatase and other extracellular kinases, promoting cell survival through activation of intracellular signaling pathways .Moreover, the binding of the ORF3 encoded protein to host-specific proteins seems to influence the pathogenesis of HEV infections .A schematic drawing of the HEV genome is described in Figure 1 .