Rapamycin and everolimus facilitate hepatitis E virus replication: Revealing a basal defense mechanism of PI3K-PKB-mTOR pathway

Zhou, Xinying; Wang, Yijin; Metselaar, Herold J.; Janssen, Harry L A; Peppelenbosch, Maikel P.; Pan, Qiuwei

doi:10.1016/j.jhep.2014.05.026

Cited by 103 publications

(87 citation statements)

References 48 publications

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“…Inhibition of the PI3K-PKBmTOR signal pathway has been shown to facilitate HEV replication (Zhou et al, 2014). Weakened immunity and increased nutritional demands during pregnancy are associated with the downregulation of PI3K-PKB-mTOR signalling and promotion of HEV infection (Zhou et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Pregnancy serum facilitates hepatitis E virus replication in vitro

Yang

et al. 2015

Journal of General Virology

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Hepatitis E virus (HEV) infection causes high mortality in pregnant women. However, the pathogenic mechanisms of HEV infection in pregnant women remain unknown. In this study, the roles of pregnancy serum in HEV infection were investigated using an efficient cell culture system. HEV infection was exacerbated by supplementing with pregnancy serum, especially theat in third trimester of pregnancy. Oestrogen receptors (ER-a and ER-b) were activated in cells supplemented with pregnancy serum and were significantly inhibited during HEV infection. Type I IFN, especially IFN-b, showed delayed upregulation in HEV-infected cells supplemented with the serum in the third trimester of pregnancy, which indicated that delayed IFN-b expression may facilitate viral replication. Results suggested that pregnancy serum accelerated HEV replication by suppressing oestrogen receptors and type I IFN in the early stage of infection.

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Section: Discussionmentioning

confidence: 99%

Pregnancy serum facilitates hepatitis E virus replication in vitro

Yang

et al. 2015

Journal of General Virology

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“…135 In this case, although HEV RNA was undetectable after bition. 136 The calcineurin inhibitors (tacrolimus, ciclosporin A) have also been shown to have a pro-proliferative effect, in contrast to mycophenolate mofetil which inhibits HEV replication in vitro. 137 In transplant recipients, the initial treatment approach should be to reduce immunosuppression if this is feasible.…”

Section: Medical Therapymentioning

confidence: 99%

Review article: hepatitis E—a concise review of virology, epidemiology, clinical presentation and therapy

Donnelly

Scobie

Crossan

et al. 2017

Aliment Pharmacol Ther

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SummaryBackground: Hepatitis E virus (HEV) is a leading cause of acute icteric hepatitis and acute liver failure in the developing world. During the last decade, there has been increasing recognition of autochthonous (locally acquired) HEV infection in developed countries. Chronic HEV infection is now recognised, and in transplant recipients this may lead to cirrhosis and organ failure.Aim: To detail current understanding of the molecular biology of HEV, diagnostic and therapeutic strategies and propose future directions for basic science and clinical research.Methods: PubMed was searched for English language articles using the key words "hepatitis E", "viral hepatitis", "autochthonous infection", "antiviral therapy", "liver transplantation", "acute", "chronic", "HEV", "genotype", "transmission" "food-borne", "transfusion". Additional relevant publications were identified from article reference lists. Future work should focus on increasing awareness of HEV infection in the developed world, emphasising the need for clinicians to have a low threshold for HEV testing, particularly in immunosuppressed patients. Patients at potential risk of chronic HEV infection must also be educated and given advice regarding prevention of infection.

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“…In vitro studies have shown that both of these calcineurin inhibitors promote HEV replication by inhibiting cyclophilins A and B, while mycophenolic acid, an inhibitor of inosine 5′ monophosphate dehydrogenase, inhibits HEV replication [98]. Rapamycin and everolimus also promote HEV replication in vitro by inhibiting mechanistic target of rapamycin (mTOR), showing that the PI3K-PKB-mTOR pathway acts as a cell restriction factor [99]. Patients given mTOR inhibitors have higher plasma concentrations of HEV RNA, but mycophenolic acid does not influence HEV replication in vivo.…”

Section: Pathogenesis Of Chronic Infection In Immunocompromised Pamentioning

confidence: 99%