Molecular biology and pathogenesis of hepatitis E virus

Chandra, Vivek; Taneja, Shikha; Kalia, Manjula; Jameel, Shahid

doi:10.1007/s12038-008-0064-1

Cited by 185 publications

(154 citation statements)

References 120 publications

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“…ORF1 occupies the 5′ two-thirds of the genome and encodes enzymes required for RNA replication. ORF2 encodes the structural protein comprising the virion capsid, and ORF3, which mostly overlaps ORF2, encodes a short protein of 114 amino acids that is required for virus egress from cells and that is proposed to perturb numerous cellular pathways (13)(14)(15). ORF2 and ORF3 proteins are translated from a single, bicistronic, subgenomic mRNA in which the ORF3 methionine initiation codon is located 11 nucleotides upstream of that of ORF2 (16).…”

mentioning

confidence: 99%

Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus–host recombinant

Shukla

Nguyen

Torian

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

286

335

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The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20–30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene.

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mentioning

confidence: 99%

Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus–host recombinant

Shukla

Nguyen

Torian

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

286

335

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“…Despite their similar names, the 5 viruses are unrelated, and they have totally different genome structures with distinct 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, including parts of Asia, the Middle East, Africa, and Mexico (1,2). HEV accounts for more than 50% of acute viral hepatitides in young adults in these regions, with a case fatality of 1-2% in regular patients and up to 20% in pregnant women.…”

mentioning

confidence: 99%

Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding

Guu

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

223

247

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Hepatitis E virus (HEV), a small, non-enveloped RNA virus in the familyHepeviridae, is associated with endemic and epidemic acute viral hepatitis in developing countries. Our 3.5-Å structure of a HEV-like particle (VLP) shows that each capsid protein contains 3 linear domains that form distinct structural elements: S, the continuous capsid; P1, 3-fold protrusions; and P2, 2-fold spikes. The S domain adopts a jelly-roll fold commonly observed in small RNA viruses. The P1 and P2 domains both adopt ␤-barrel folds. Each domain possesses a potential polysaccharide-binding site that may function in cell-receptor binding. Sugar binding to P1 at the capsid protein interface may lead to capsid disassembly and cell entry. Structural modeling indicates that native T ‫؍‬ 3 capsid contains flat dimers, with less curvature than those of T ‫؍‬ 1 VLP. Our findings significantly advance the understanding of HEV molecular biology and have application to the development of vaccines and antiviral medications.capsid ͉ HEV V iral hepatitis is principally caused by 5 distinct viruses named hepatitis A-E. Despite their similar names, the 5 viruses are unrelated, and they have totally different genome structures with distinct 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, including parts of Asia, the Middle East, Africa, and Mexico (1, 2). HEV accounts for more than 50% of acute viral hepatitides in young adults in these regions, with a case fatality of 1-2% in regular patients and up to 20% in pregnant women.Given the lack of a robust cell culture system, and because HEV is not closely related to any other well-characterized virus, little is known about the molecular biology of HEV or its strategy for replication (1). HEV is a small, non-enveloped virus with a 7.2 kb, positive-sense RNA genome. Its genomic RNA is polyadenylated and contains 3 ORFs. Located near the 5Ј-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 3Ј-end. ORF3, which partially overlaps with the other 2 ORFs, codes for an immunogenic protein of unknown function. HEV was originally classified in the Caliciviridae family because of its structural similarity to other caliciviruses; however, it is now the sole member of the Hepeviridae family. The genomic RNA of HEV exhibits several distinct features compared to the genomic RNA of caliciviruses, including a methylated cap at the 5Ј-end and an ORF1 with functional domains arranged in a different order (1, 3).Previous studies of HEV assembly have primarily focused on the overexpression of viral proteins. 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 assem...

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“…NS: not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. birth. However, the mechanism of virusinvasioninto theepithelium of the oropharynx and then into the liverstill remains unknown [8,9,34].…”

Section: B)mentioning

confidence: 99%

Antiviral Activity of Selected Indian Medicinal Herbs Against Hepatitis E Virus (Hev) in the Established Porcine Cell Model

Roy¹,

Kanwar²,

Langerholc³

2017

J Res Educ Indian Med - ISSN 0970-7700

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Abstract:Background: It is known that hepatitis E virus (HEV) is zoonotically transmitted to humans and while other forms of hepatitis have been in focus for drug and vaccine development, HEV related mortality in case of pregnant women can reach upto 20%. Methods: HEV proteins, were successfully extracted from 22 pig stool samples and the presence of HEV capsid antigen encoded by the open reading frame 2 (ORF2) was confirmed using dot blot and western blotting in 4 samples. HEV samples were inoculated in pig epithelial cells (CLAB) and pig macrophage (POM2) to develop an in vitro model for observing the cytopathic effects (CPE). The HEV infected cell cultures were subjected to water: methanol (95:5) extracts from Kaempfaria galanga (Galangal), Mimosa pudica (Touch me not), Coleus aromaticus (Doddapatre)and Paederia foetida (Stinkvine).Results:We showed that incubation of 56 μg/mL HEV samples for 3 hours induced characteristic growth patterns in cells until 4 passages. We also found that extracts of K. galanga significantly (p<0.001) increased cell viability in CLAB cells while other extracts showed cytotoxic effects. In the preventive study (treatments of cells with extracts followed by infection of cells with viral proteins), both 10 -2 and 10 -3 dilutions of K. galanga extracts significantly (p<0.001) prevented a decrease in cell viability of CLAB cells after HEV infection. The 10 -2 dilution of C. aromaticus (p<0.01) and 10 -3 dilution of K. galanga was the only effective (p<0.001) extract in case of HEV infected POM2 cells. Conclusion: A new in vitro cell culture model based on CLAB and POM2 cells has been developed to study HEV.We are also the first to report the activity of these medicinal extracts against HEV in a cell culture model. Extracts of K. galanga and P. foetida showed a promising anti-viral activity and the potential to be used as a natural therapy against HEV.

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Molecular biology and pathogenesis of hepatitis E virus

Cited by 185 publications

References 120 publications

Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus–host recombinant

Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus–host recombinant

Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding

Antiviral Activity of Selected Indian Medicinal Herbs Against Hepatitis E Virus (Hev) in the Established Porcine Cell Model

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