Hepatitis C virus infection induces endoplasmic reticulum stress and apoptosis in human fetal liver stem cells

Abstract

The cellular mechanisms by which hepatitis C virus (HCV) replication might mediate cytopathic effects are controversial and not entirely clear. In this study, we found that blood-borne HCV (bbHCV) infection could lead to endoplasmic reticulum (ER)-stress and mitochondria-related/caspase-dependent apoptosis at the early stages of infection based on use of the highly efficient bbHCV cell culture model established previously. Sections of bbHCV-infected human fetal liver stem cells (hFLSCs) revealed convolution and nonlinear ER, cell vacuolization, swelling of mitochondria, and numerous double membrane vesicles (DMVs). The percentage of apoptotic hFLSCs infected by bbHCV reached 29.8% at 16 h postinfection, and the amount of cytochrome c increased remarkably in the cytosolic protein fraction. However, over time, apoptosis was inhibited due to the activation of NF-B. The expression of NF-B-p65, Bcl-xL, XIAP, and c-FLIPL in hFLSCs was increased significantly 24 h after in infection by bbHCV. The accelerated cell death cycles involving apoptosis, regeneration and repair by bbHCV infection might give rise to the development of cirrhosis, and ultimately to hepatocellular carcinogenesis.We then explored the role ER stress plays in cells apoptosis. The expression of ER stress-related proteins, GRP78 and phosphorylated eIF2-alpha were assessed in bbHCV-infected cells. The overexpression of GRP78 and phosphorylated eIF2-alpha strongly suggested that bbHCV infection could induce ER stress as an early cell DiscussionHCV infection induced CPE is part of the infection process. Whether the established infection model could simulate and undergo CPE similar to lesions observed in hepatitis patients could be a measure of the model's success. The presentation of HCV-induced CPE is vital in cell culture systems, and could contribute to the

The Role of Bcl-xL Protein in Viral Infections

“…On the other hand, Bcl-xL may also be co-responsible for HCV-induced oncogenesis. Research by Guo et al [ 57 ] on human fetal liver stem cells (hFLSCs) infected with HCV has revealed nuclear factor-ĸB (NF-ĸB)-dependent mechanisms that counteract HCV-induced apoptosis at the late stage of infection. One of the cell survival-promoting events was the upregulation of intracellular Bcl-xL [ 57 ].…”

“…Research by Guo et al [ 57 ] on human fetal liver stem cells (hFLSCs) infected with HCV has revealed nuclear factor-ĸB (NF-ĸB)-dependent mechanisms that counteract HCV-induced apoptosis at the late stage of infection. One of the cell survival-promoting events was the upregulation of intracellular Bcl-xL [ 57 ]. Meanwhile, previous studies had found the overexpression of Bcl-xL in HCCs and suggested the contribution of its anti-apoptotic activity to HCC survival under various stress conditions, and to hepatocellular carcinoma development [ 58 , 59 ].…”

Total astragalosides decrease apoptosis and pyroptosis by inhibiting enterovirus 71 replication in gastric epithelial cells

“…Apoptosis is an autonomous type of PCD (9). EV71, hepatitis B and C and other viruses induce apoptosis (7,37,38). Viruses tend to use host cells to induce apoptosis of tissue or immune cells to infect the body (39).…”

Gypenoside Inhibits Bovine Viral Diarrhea Virus Replication by Interfering with Viral Attachment and Internalization and Activating Apoptosis of Infected Cells

“…Not only that, but some viruses can also trigger cells to produce Bcl-2. Hepatitis C virus and human T-cell leukemia virus (HTLV) both induce Bcl-XL expression, and HTLV also induces Bcl-2 expression by involving the activation of NFκB [ 34 , 35 , 36 ]. In line with this, we observed increased activation of Bcl-2 in BVDV-infected cells, suggesting that it is involved in the observed induction of Bcl-2.…”