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. 2019 Jan;9(1):a031724. doi: 10.1101/cshperspect.a031724

Figure 2.

Figure 2.

Genomic organization of hepatitis E virus (HEV). The genome of HEV is ∼7.2 kb in length and is composed of a single-stranded positive-sense RNA molecule. The genome contains a 7-methylguanosine RNA cap at the 5′ end and is polyadenylated at the 3′ terminus. There are three conserved open reading frames (ORFs) found in all known HEV strains: ORF1, ORF2, and ORF3. ORF1 encodes the nonstructural polyproteins with putative functional domains including methyltransferase (Met), Y domain, papain-like cysteine protease (PCP), hypervariable region (HVR), helicase (Hel), and RNA-dependent RNA polymerase (RdRp). ORF2 encodes the capsid structural protein. ORF3 encodes a multifunctional phosphoprotein (also known as VP13). ORF2 and ORF3 proteins are translated from a bicistronic subgenomic RNA 2.2 kb in length. In addition to these three ORFs, the genotype (gt)1 HEV encodes an ORF4, which generates a protein from an internal ribosome entry site (IRES)-like element in response to endoplasmic reticulum (ER) stress. This ORF4 protein is a viral replication enhancer. A number of RNA structural elements within the HEV genome contribute to RNA packaging (5′ RNA stem loops), translation of ORF2, ORF3 (junction region CREs), and ORF4 (IRES-like element), and in binding of the genomic RNA to the RdRp (3′ CRE). Positions and lengths of ORFs and indicated features are based on the prototypical gt1 HEV (Sar55 strain) sequence (GenBank accession number AF444002.1).