"However, HEV infection may occasionally cause severe liver dysfunction, fulminant hepatitis, and liver failure in some patients with an underlying disease (Kamar et al., 2012; Suzuki et al., 2002). Furthermore, HEV genotype 3 can lead to chronic hepatitis and liver cirrhosis in immunocompromised patients such as solid-organ transplant (SOT) recipients (Kamar et al., 2008), patients with human immunodeficiency virus infection (Dalton et al., 2009), and patients with hematologic cancers receiving chemotherapy (Ollier et al., 2009). Various studies have investigated the presence of HEV infection in SOT recipients in European and American countries but not yet in Japan. "
"Several studies have been demonstrated that immunosuppressed cases, such organ transplant recipients, cases with HIV infection and patients with hematological malignancies and lymphoma , are at risk of HEV infection. "
[Show abstract][Hide abstract] ABSTRACT: Hepatitis E virus (HEV) is a small, single-stranded, non-enveloped RNA virus and belongs to the genus Hepevirus in the Hepeviridae family. Currently, the HEV infection is the most frequent cause of acute hepatitis in the world. In recent years, some studies have been demonstrated that immunosuppressed cases, such organ transplant recipients, cases with HIV infection and patients with hematological malignancies are at risk of HEV infection. But it is not clear whether HEV infection is a major concern in HIV infected patients or not? The answer has considerable significance, because HIV and HEV infection are now both highly endemic in many parts of the world. The purpose of this review is to provide data on the prevalence of HEV infection in HIV infected patients for determination of the significance of HEV/HIV co-infection.
"In Western countries, HEV infection of healthy individuals almost exclusively remains subclinical and otherwise causes an acute and self-limiting infection in immune-competent individuals with low mortality rates . In contrast, patients with HEV infection in immunocompromised individuals that include organ transplantation recipients , HIV patients  and cancer patients receiving chemotherapy  have a substantially high risk of developing chronic hepatitis. The use of immunosuppressants, such as rapalogs, in organ transplant recipients to prevent rejection is associated with substantial pathology and in particular an increased risk of developing chronic hepatitis with substantial graft loss and mortality rates . "
[Show abstract][Hide abstract] ABSTRACT: Background & aims:
Humans are frequently exposed to hepatitis E virus (HEV). Nevertheless, the disease mainly affects pregnant women and immunocompromised individuals. Organ recipients receiving immunosuppressants, such as rapalogs, to prevent rejection have a high risk for developing chronic hepatitis following HEV infection. Rapalogs constitute potent inhibitors of mTOR including rapamycin and everolimus. As a master kinase, the mechanism-of-action of mTOR is not only associated with the immunosuppressive capacity of rapalogs but is also tightly regulated during pregnancy because of increased nutritional demands.
We thus investigated the role of mTOR in HEV infection by using two state-of-the-art cell culture models: a subgenomic HEV containing luciferase reporter and a full-length HEV infectious cell culture system.
In both subgenomic and full-length HEV models, HEV infection was aggressively escalated by treatment of rapamycin or everolimus. Inhibition of mTOR was confirmed by Western blot showing the inhibition of its downstream target, S6 phosphorylation. Consistently, stable silencing of mTOR by lentiviral RNAi resulted in a significant increase in intracellular HEV RNA, suggesting an antiviral function of mTOR in HEV infection. By targeting a series of other up- and downstream elements of mTOR signaling, we further revealed an effective basal defense mechanism of the PI3K-PKB-mTOR pathway against HEV, which is through the phosphorylated eIF4E-binding protein 1 (4E-BP1), however independent of autophagy formation.
The discovery that PI3K-PKB-mTOR pathway limits HEV infection through 4E-BP1 and acts as a gate-keeper in human HEV target cells bears significant implications in managing immunosuppression in HEV-infected organ transplantation recipients.
Journal of Hepatology 05/2014; 61(4). DOI:10.1016/j.jhep.2014.05.026 · 11.34 Impact Factor
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