Hepatitis E Viruses (HEV):
HEV is a small, non-enveloped, icosahedral
virus with a positive-sense RNA genome of 7.2 kb. Its genomic RNA is polyadenylated
and contains three open reading frames (ORFs). HEV was originally classified
in the Caliciviridae family because of its structural similarity to other
caliciviruses. However, it is now regarded as the sole member of the Hepevirus genus.
The genomic RNA of HEV exhibits several distinct features compared to the
genomic RNA of caliciviruses, including a methylated cap at the 5'-end and
an ORF1 with functional domains arranged in a different order.
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The crystal structure of HEV has been determined at 3.5-Å resolution (Structure
of the hepatitis E virus-like particle suggests mechanisms for virus assembly
and receptor binding. PNAS USA July 21, 2009).
The capsid protein of this virus contains three linear domains that form distinct
structural elements:
- S, the continuous capsid
- P1, three-fold protrusions
- P2, two-fold spikes
Each domain possesses a potential polysaccharide-binding site that may function in receptor binding. Receptor binding to P1 at the capsid protein interface may lead to capsid disassembly and cell entry.
The symptoms of HEV are typical of acute viral hepatitis and the infection
follows a natural history that is similar to that of hepatitis A. Up to 43.5%
of urban sewage samples collected in industrialized countries may be positive
for HEV, suggesting that HEV may be more prevalent than previously
considered in industrialized countries and that variants of the virus circulate
simultaneously in most countries (Emerg Infect Dis. 2003 9(4):448-54).
Primate studies indicate faecal-oral (waterborne) transmission of the virus.
HEV is endemic in S.E. Asia, ex 'USSR', India, Mid-East, Africa and C. America.
~1% of US blood donors have anti-HEV antibodies. Large epidemics with person
to person spread have been known to occur. Normal course of infection seems
to be an acute but relatively benign illness (c.f. HAV), except in pregnant
women where there is 15-30% mortality. Recombinant vaccines are currently being
prepared.
A closely related virus, swine hepatitis E virus (swine HEV), was recently
identified in pigs. Swine HEV crossreacts with antibody to the human HEV capsid
antigen & is a ubiquitous agent in pigs. The putative capsid gene (ORF2)
of swine HEV shares about 80% sequence identity at the nucleotide level and
90-92% identity at the amino acid level with human HEV strains.
Antibodies to HEV also indicate infection in up to 60% of rats and other rodents
in the USA.
The possible medical significance of these findings remains unclear at present.
A recombinant HEV vaccine has recently proved to be safe and effective in
a phase 2 clinical trial (Safety
and Efficacy of a Recombinant Hepatitis E Vaccine. 2007 NEJM 356: 895-903).
Expert Reviews in Molecular Medicine: Molecular
biology and pathogenesis of hepatitis E virus
© MicrobiologyBytes 2009.