Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: (99)00132-5h.htm (shortcode: fig005sjd); 6 December 1999
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Genome organisation of hepatitis E virus

Shahid Jameel

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Figure 5. Genome organisation of hepatitis E virus. (a) The hepatitis E virus (HEV) genome is a ~7.5 kb polyadenylated RNA. At its 5' and 3' termini, the viral RNA carries two short (26- and 68-nucleotide) untranslated regions (UTRs) that form conserved stem–loop structures. A 58-nucleotide conserved region within ORF1 can also fold into two hairpin loops. Within ORF1, the viral RNA also carries a sequence stretch with homology to the junction sequences found in Sindbis virus (an alphavirus). It is positive-sense and includes three open reading frames (ORFs): (b) ORF1 (~5 kb), encoding a putative nonstructural polyprotein (nsP) that includes domains found in viral methyltransferases (MeT), papain-like cysteine proteases (Pr), viral RNA helicases (Hel) and viral RNA-dependent RNA polymerases (RdRp); (c) ORF2 (~2 kb), encoding the major viral capsid protein (pORF2 and its glycosylated form gpORF2), carrying a signal peptide at its N-terminal end and three N-linked glycosylation sites [Asn137, Asn310 and Asn562, of which Asn310 (boxed) appears to be the major site of N-linked glycan addition]; (d) ORF3, encoding a small protein (pORF3) with two hydrophobic domains in its N-terminal half, which includes a polycysteine [Poly(Cys)] region, and proline-rich [Poly(Pro)] sequences in its C-terminal half. pORF3 is phosphorylated at a single (Ser80) amino acid by the cellular mitogen-activated protein kinase (MAPK), associates with the cytoskeleton through its N-terminal end and with proteins carrying the src-homology 3 (SH3) motifs through its C-terminal end. (e) Three HEV-specific RNAs have been found in the livers of experimentally infected monkeys: a genomic ~7.5 kb [covalently capped with a 7-methylguanosine (m⁷G) nucleotide] and two subgenomic ~3.7 kb and ~2 kb species. This indicates a replication scheme similar to alphaviruses in which the structural genes are translated from subgenomic RNAs generated late in viral replication, but unlike other positive-stranded RNA viruses such as poliovirus or hepatitis C virus in which the genomic RNA is directly translated into the complete viral polyprotein (fig005sjd).

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