Hepatitis E virus, discovered in 1983 by immune electron microscopy and first cloned in 1990.
Structure of Hepatitis E Virus
- HEV is classified in the Calciviridae family because of its structural similarity to other calciviruses; however, it is now the sole member of the Hepeviridae family.
- The virus is non enveloped (naked) with icosahedral symmetry measuring 27-30 nm diameter.
- The genome is single stranded RNA genome with positive polarity and measure about 7.2 kb in length.
- Both immune and negative stain electron microscopy of human stool specimens have showed that the diameter of HEV is about 32 nm.
- The surface of the virion has obvious spikes that are slightly less pronounced than those of Norovirus, but is clearly distinct from the smooth, featureless surface of the hepatitis A virus.
- Based on genome sequences, five major genotypes have been identified.
- The circulation of genotypes 1 and 2 viruses is maintained among only humans, while those of genotypes 3 and 4 are found in human as well as animals.
- The viruses of genotype 5 are of avian origin, thought to be noninfectious to humans.
- Although four of the five genotypes infect human ,only one HEV serotype has been found in human.
Genome of Hepatitis E Virus
- The HEV genome is a single-stranded, positive-sense RNA molecule and 7.2 kb in size.
- Genomic RNA is polyadenylated and contains 3 ORFs.
- ORF1 encodes the nonstructural proteins, ORF2 encodes the capsid protein, and ORF3 encodes a small multifunctional protein.
- The ORF2 and ORF3 proteins are translated from a single, bicistronic mRNA.
- Located near the 5′-end, ORF1 encodes a non-structural polyprotein with multiple functional domains, including those for methyltransferase, protease, helicase, and polymerase.
- The viral capsid protein (CP) is encoded by ORF2 near the 3′-end.
- ORF3, which partially overlaps with the other 2 ORFs, codes for an immunogenic protein of unknown function.
- ORF3 encodes a 113 or 114 aa phosphoprotein, depending upon the genotype.
- The ORF2 capsid protein, HEV-CP, contains a total of 660 amino acid residues.
- At the HEV-CP N terminus is a signal peptide followed by an arginine-rich domain that potentially play a role in viral RNA encapsidation during assembly.
- HEV-CP is a key antigen that stimulates the host immune response, and 6 antigenic domains have been identified.
- One neutralization site has been mapped to the polypeptide region between amino acids 452 and 617.
Image: Schematic illustration of non-enveloped and quasi-enveloped HEV particles as well as enveloped virus. The putative model of quasi-enveloped HEV virion includes ORF3 product in its envelope as the existence of pORF3 has been confirmed by capturing quasi-enveloped HEV virion with anti-pORF3 antibodies and further supported by prediction of a putative transmembrane region in the N-terminal of pORF3.