MicrobiologyBytes

Viral hepatitis is mostly caused by five distinct viruses named hepatitis A–E. Despite their names, the five viruses are unrelated, with totally different genome structures and replication mechanisms. Hepatitis E virus (HEV) is responsible for endemic hepatitis as well as sporadic epidemics of acute, enterically transmitted hepatitis in the developing world. HEV accounts for more than 50% of acute viral hepatitis in young adults in these regions, with a case fatality of 1–2% in regular patients and up to 20% in pregnant women. Because there is no robust cell culture system for this virus, and because it is not closely related to any other well-characterized virus, little is known about the molecular biology of HEV or its strategy for replication.

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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A recent paper in PNAS describes the crystal structure of HEV 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. These findings significantly advance the understanding of HEV and are useful for the development of vaccines and antiviral medications.