Hepatitis C virus core protein does not inhibit apoptosis in human hepatoma cells

Dumoulin, Franz Ludwig; Bussche, A vsn dem; Söhne, J; Sauerbruch, Tilman; Spengler, Ulrich

doi:10.1046/j.1365-2362.1999.00559.x

Cited by 31 publications

(22 citation statements)

References 30 publications

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“…Coredependent inhibition of TNF-α- [71] and CD95Ligand-induced apoptosis [72] has been described in a hepatoma cell line. In other models, overexpressed HCV core protein did not prevent CD95Ligand-induced apoptosis in hepatoma cells [73] or transgenic mice expressing HCV core protein, E1, E2 and NS2, respectively. HCV core protein inhibits CD95Ligand-mediated apoptosis by prevention of cytochrome C release from mitochondria and consecutive activation of caspase-9, -3 and -7 [74] .…”

Section: Hcv Core Proteinmentioning

confidence: 88%

Hepatitis C virus infection and apoptosis

Fischer

Baumert²,

Blum³

2007

WJG

117

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Section: Hcv Core Proteinmentioning

confidence: 88%

Hepatitis C virus infection and apoptosis

Fischer

Baumert²,

Blum³

2007

WJG

117

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“…The hepatitis C virus (HCV) core protein is similarly localized (2,6,54). Moreover, expression of the HCV core protein causes apoptosis induction in some, but not all, transfected cells (6,25,29). The determinants of lipid droplet localization of the HCV core protein have been mapped to amphipathic ␣-helices whose primary sequence is homologous to plant oleosins, which associate with lipid droplets (30).…”

Section: Discussionmentioning

confidence: 99%

Reovirus Outer Capsid Protein μ1 Induces Apoptosis and Associates with Lipid Droplets, Endoplasmic Reticulum, and Mitochondria

Coffey

Sheh

Kim

et al. 2006

J Virol

105

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The mechanisms by which reoviruses induce apoptosis have not been fully elucidated. Earlier studies identified the mammalian reovirus S1 and M2 genes as determinants of apoptosis induction. However, no published results have demonstrated the capacities of the proteins encoded by these genes to induce apoptosis, either independently or in combination, in the absence of reovirus infection. Here we report that the mammalian reovirus 1 protein, encoded by the M2 gene, was sufficient to induce apoptosis in transfected cells. We also found that 1 localized to lipid droplets, endoplasmic reticulum, and mitochondria in both transfected cells and infected cells. Two small regions encompassing amphipathic ␣-helices within a carboxyl-terminal portion of 1 were necessary for efficient induction of apoptosis and association with lipid droplets, endoplasmic reticulum, and mitochondria in transfected cells. Induction of apoptosis by 1 and its association with lipid droplets and intracellular membranes in transfected cells were abrogated when 1 was coexpressed with 3, with which it is known to coassemble. We propose that 1 plays a direct role in the induction of apoptosis in infected cells and that this property may relate to the capacity of 1 to associate with intracellular membranes. Moreover, during reovirus infection, association with 3 may regulate apoptosis induction by 1.

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“…13 Dumoulin et al reported that HCV core protein or HCV E2 protein individually do not prevent TNF-␣ or Fas induced-apoptosis in transient transfected HepG2 cells. 14 Lasarte et al reported that a recombinant adenovirus encoding HCV core and E1 proteins protects liver cells from cytokine-induced hepatocellular damage in experimental models of TNF-mediated hepatic injury. 15 These data suggest the possibility that E1 with or without E2 has an antiapoptotic effect.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis†

et al. 2005

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We developed hepatitis C virus (HCV) core-E1-E2 and HCV core transgenic mice on a common genetic background to assess the contribution of HCV structural proteins to hepatocarcinogenesis. Eight-week-old core-E1-E2, core, and nontransgenic mice inbred on the FVB؋C57Bl/6 background were treated with diethylnitrosamine (DEN) and sacrificed at 32 weeks old. Proliferation and apoptosis were assessed by immunohistochemistry. H epatitis C virus (HCV) infects an estimated 170 million people worldwide, and 2.7 million people in the United States harbor active HCV infection. 1 Chronic HCV infection has been independently established as a leading cause of hepatocellular carcinoma (HCC). Unlike hepatitis B virus (HBV), the RNA genome of HCV does not integrate into the host chromosome. HCV-related hepatocarcinogenesis is, therefore, not likely to involve insertional mutagenesis. Rather, it has been hypothesized that HCV produces HCC through the cumulative effects of chronic infection, injury and repair. Whether HCV proteins are directly oncogenic has not been established. Unfortunately, the lack of an appropriate small animal model of HCV has impeded progress in defining the molecular mechanisms of HCV-induced carcinogenesis.We originally developed an HCV transgenic mouse model encoding the core, E1, and E2 structural proteins under the control of the albumin promoter on the FVB background; despite high-level protein expression, this model did not develop hepatic pathology. 2 However, more recently, Moriya et al. developed a transgenic mouse model on the C57Bl/6 background that overexpresses Abbreviations: HCV, hepatitis C virus; DEN, diethylnitrosamine; HCC, hepatocellular carcinoma; AI, apoptotic index; PI, proliferation index. From the

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Hepatitis C virus core protein does not inhibit apoptosis in human hepatoma cells

Cited by 31 publications

References 30 publications

Hepatitis C virus infection and apoptosis

Hepatitis C virus infection and apoptosis

Reovirus Outer Capsid Protein μ1 Induces Apoptosis and Associates with Lipid Droplets, Endoplasmic Reticulum, and Mitochondria

Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis†

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