title: Hepatitis e: molecular virology and pathogenesis.
abstract: Hepatitis E virus is a single, positive-sense, capped and poly A tailed RNA virus classified under the family Hepeviridae. Enteric transmission, acute self-limiting hepatitis, frequent epidemic and sporadic occurrence, high mortality in affected pregnants are hallmarks of hepatitis E infection. Lack of an efficient culture system and resulting reductionist approaches for the study of replication and pathogenesis of HEV made it to be a less understood agent. Early studies on animal models, sub-genomic expression of open reading frames (ORF) and infectious cDNA clones have helped in elucidating the genome organization, important stages in HEV replication and pathogenesis. The genome contains three ORF's and three untranslated regions (UTR). The 5' distal ORF, ORF1 is translated by host ribosomes in a cap dependent manner to form the non-structural polyprotein including the viral replicase. HEV replicates via a negative-sense RNA intermediate which helps in the formation of the positive-sense genomic RNA and a single bi-cistronic sub-genomic RNA. The 3' distal ORF's including the major structural protein pORF2 and the multifunctional host interacting protein pORF3 are translated from the sub-genomic RNA. Pathogenesis in HEV infections is not well articulated, and remains a concern due to the many aspects like host dependent and genotype specific variations. Animal HEV, zoonosis, chronicity in immunosuppressed patients, and rapid decompensation in affected chronic liver diseased patients warrants detailed investigation of the underlying pathogenesis. Recent advances about structure, entry, egress and functional characterization of ORF1 domains has furthered our understanding about HEV. This article is an effort to review our present understanding about molecular biology and pathogenesis of HEV.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Subrat K
authors.initials: SK
authors.lastname: Panda
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Satya P K
authors.initials: SP
authors.lastname: Varma
keywords: DUB, deubiquitinating; ELISPOT, enzyme-linked immunosorbent spot; EMSA, electrophoretic mobility shift assay; ER, endoplasmic reticulum; Hepeviridae; NTP, nucleoside triphosphate; ORF, open reading frames; RdRp, RNA dependent RNA polymerase; UTR, untranslated region; open reading frames; pathogenesis