Figure 1. Geographical distribution of hepatitis E virus (HEV) endemicity. The blue-shaded areas represent disease-endemic regions.

Figure 2. HEV-like particles. An immunoelectron micrograph of HEV from the stool of a patient acutely infected with the Burmese isolate. The picture shows 27–34 nm diameter particles aggregated with antibodies present in the serum of a patient infected with HEV.

Figure 3. Genomic organization of HEV. The positions of the genes in the HEV genome are indicated. The genome of HEV, approximately 7.2 kb polyadenylated ribonucleic acid (RNA), contains three open reading frames (ORFs). ORF1 (approximately 5 kb) encodes a putative nonstructural polyprotein, which includes domains found in viral methyltransferases, papain-like cysteine proteases, viral RNA helicases and viral RNA polymerases. ORF2 (approximately 2 kb) encodes the major capsid protein and carries a signal peptide at its N-terminal end and three N-linked glycosylation sites (Asn137, Asn310 and Asn562). ORF3 encodes a small protein with two hydrophobic domains in its N-terminal half, which includes a polycysteine region and a proline-rich transmembrane sequence.

Figure 4. Proposed model of HEV replication and capsid assembly. The virus shown as (¨) enters the cell by an unknown mechanism. After uncoating, the viral genomic RNA is translated into nonstructural (NS) gene products like RNA-dependent RNA polymerase (RdRP), helicase, methyltransferase (methyltr), shown as () and antigenomic RNA shown as (-----). Genomic RNA and sub-genomic mRNAs are produced from the anti-genomic RNA. Viral structural proteins, pORF2 and possibly pORF3 are translated from subgenomic mRNAs. pORF2 is processed in the endoplasmic reticulum and transported to the cis-Golgi complex. Assembly of the virion occurs by the encapsidation of genomic RNA and its association with pORF2 and pORF3. Progeny virions thus formed are ready to exit the cell.