Hepatitis E Virus Inhibits Type I Interferon Induction by ORF1 Products

Nan, Yuchen; Yu, Ying; Ma, Zexu; Khattar, Sunil K.; Fredericksen, Brenda L.; Zhang, Yan‐Jin

doi:10.1128/jvi.01935-14

Cited by 114 publications

(154 citation statements)

References 54 publications

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“…As different studies have reported that HEV is able to counteract the IFN‐stimulated gene (ISG) response in human liver cells,34, 35 we next investigated the viral restriction of the IFN pathway by determination of ISG expression after HEV transfection in placental‐derived cells. JEG‐3 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Hepatitis E virus replication and interferon responses in human placental cells

Knegendorf

Drave

Thi

et al. 2018

Hepatology Communications

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Hepatitis E virus (HEV) is a member of the genus Orthohepevirus in the family Hepeviridae and the causative agent of hepatitis E in humans. HEV is a major health problem in developing countries, causing mortality rates up to 25% in pregnant women. However, these cases are mainly reported for HEV genotype (gt)1, while gt3 infections are usually associated with subclinical courses of disease. The pathogenic mechanisms of adverse maternal and fetal outcome during pregnancy in HEV‐infected pregnant women remain elusive. In this study, we observed that HEV is capable of completing the full viral life cycle in placental‐derived cells (JEG‐3). Following transfection of JEG‐3 cells, HEV replication of both HEV gts could be observed. Furthermore, determination of extracellular and intracellular viral capsid levels, infectivity, and biophysical properties revealed production of HEV infectious particles with similar characteristics as in liver‐derived cells. Viral entry was analyzed by infection of target cells and detection of either viral RNA or staining for viral capsid protein by immunofluorescence. HEV gt1 and gt3 were efficiently inhibited by ribavirin in placental as well as in human hepatoma cells. In contrast, interferon‐α sensitivity was lower in the placental cells compared to liver cells for gt1 but not gt3 HEV. Simultaneous determination of interferon‐stimulated gene expression levels demonstrated an efficient HEV‐dependent restriction in JEG‐3. Conclusion: We showed differential tissue‐specific host responses to HEV genotypes, adding to our understanding of the mechanisms contributing to fatal outcomes of HEV infections during pregnancy. Using this cell‐culture system, new therapeutic options for HEV during pregnancy can be identified and evaluated. (Hepatology Communications 2018;2:173–187)

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Section: Resultsmentioning

confidence: 99%

Hepatitis E virus replication and interferon responses in human placental cells

Knegendorf

Drave

Thi

et al. 2018

Hepatology Communications

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show abstract

“…To date, the role of viral macro domains has been demonstrated in the modification of cellular response to viral infection (Nan et al, 2014;Nargi-Aizenman et al, 2002;Tan et al, 2009), as a possible RNA recruitment factor (Malet et al, 2009), or in minus-strand synthesis, P23 processing and/or viral replication (LaStarza et al, 1994a(LaStarza et al, , 1994bLulla et al, 2011). The molecular mechanism or biochemical function behind this role is not well understood.…”

Section: Proteinmentioning

confidence: 97%

Structural and biophysical analysis of sequence insertions in the Venezuelan Equine Encephalitis Virus macro domain

et al. 2015

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“…2). As antagonists of IFN type I induction, two domains in the HEV ORF1, X and papain-like cysteine protease domain (PCP), were identified by Nan et al (32). Interestingly, in vivo studies with HEV-and HCVinfected chimpanzees were also conducted to compare the innate immune responses of these two viruses.…”

Section: Discussionmentioning

confidence: 99%