The Hepatitis C Virus Core Protein Interacts with NS5A and Activates Its Caspase-Mediated Proteolytic Cleavage

Goh, Phuay-Yee; Lim, Soh Fong; Lim, Seng Gee; Tan, Yee-Joo; Hong, Wan Jin

doi:10.1006/viro.2001.1195

Cited by 54 publications

(39 citation statements)

References 52 publications

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“…2D; compare lanes 9 and 11 with lanes 15, 17, 21, and 23). This result was likely due to apoptotic hypersensitivity caused by core protein, as previously described (57,58). In this regard, it is worthy to note that core was shown to enhance apoptotic effect of TRAIL by augmenting release of cytochrome c into cytosol (33).…”

Section: Discussionsupporting

confidence: 62%

E2 of Hepatitis C Virus Inhibits Apoptosis

Lee

Kim

et al. 2005

The Journal of Immunology

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Hepatitis C virus (HCV) is the major causative agent of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, and can be involved in very long chronic infections up to 30 years or more. Therefore, it has been speculated that HCV possesses mechanisms capable of modulating host defense systems such as innate and adaptive immunity. To investigate this virus-host interaction, we generated HCV replicons containing various HCV structural proteins and then analyzed the sensitivity of replicon-containing cells to the apoptosis-inducing agent, TRAIL. TRAIL-induced apoptosis was monitored by cleavage of procaspase-3 and procaspase-9 as well as that of their substrate poly(ADP-ribose) polymerase. TRAIL-induced apoptosis was inhibited in cells expressing HCV E2. Moreover, expression of HCV E2 enhanced the colony forming efficiency of replicon-containing cells by 25-fold. Blockage of apoptosis by E2 seems to be related to inhibition of TRAIL-induced cytochrome c release from the mitochondria. Based on these results, we propose that E2 augments persistent HCV infection by blocking host-induced apoptosis of infected cells.

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Section: Discussionsupporting

confidence: 62%

E2 of Hepatitis C Virus Inhibits Apoptosis

Lee

Kim

et al. 2005

The Journal of Immunology

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“…DGAT1 Acts as a Connector between NS5A and Core-The interaction between NS5A and core is important for viral assembly (3,18). As they both interact with DGAT1, we postulated that DGAT1 may bridge the interaction of the two viral proteins.…”

Section: Ns5amentioning

confidence: 93%

Diacylglycerol Acyltransferase-1 Localizes Hepatitis C Virus NS5A Protein to Lipid Droplets and Enhances NS5A Interaction with the Viral Capsid Core

Camus

Herker

Modi

et al. 2013

Journal of Biological Chemistry

118

108

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Background:The NS5A protein regulates HCV assembly by localizing to lipid droplets. Results: The triglyceride-synthesizing enzyme DGAT1 binds NS5A, enhances interactions of NS5A with the viral capsid core, and enables lipid droplet localization of NS5A. Conclusion: DGAT1 functions as a cellular "hub" for HCV proteins to access lipid droplets. Significance: DGAT1 inhibitors suppress HCV assembly by preventing NS5A access to DGAT1-generated lipid droplets.

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“…Amino-terminal NS5A-Gal4 fusion proteins have trans-activating properties (Tanimoto et al, 1997). Although intact NS5A is cytoplasmic and membrane-bound (Brass et al, 2002), caspase-mediated cleavage exposes a cryptic nuclear localization signal (Ide et al, 1996) and leads to NS5A nuclear localization, where it functions as a PKAregulated transcription factor (Satoh et al, 2000b;Goh et al, 2001). Truncated versions of NS5A modulate transcriptional.…”

Section: Ns5amentioning

confidence: 99%

Viral hepatitis and liver cancer: the case of hepatitis C

2006

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Chronic infection with the hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC) worldwide. The pathogenesis of HCC in HCV infection has extensively been analysed. Hepatitis C virus-induced chronic inflammation and the effects of cytokines in the development of fibrosis and liver cell proliferation are considered as one of the major pathogenic mechanisms. Increasing experimental evidence suggests that HCV contributes to HCC by directly modulating pathways that promote the malignant transformation of hepatocytes. Hepatitis C virus is an RNA virus that does not integrate into the host genome but HCV proteins interact with many host-cell factors well beyond their roles in the viral life cycle and are involved in a wide range of activities, including cell signaling, transcription, cell proliferation, apoptosis, membrane rearrangements, vesicular trafficking and translational regulation. At least four of the HCV gene products, namely HCV core, NS3, NS4B and NS5A, have been shown to exhibit transformation potential in tissue culture and several potentially oncogenic pathways have been shown to be altered by the expression of HCV proteins. Both HCV core and NS5A induce the accumulation of wild-type b-catenin and the Wnt-b-catenin pathway emerges as a common target for HCV (and HBV) in human HCCs, also independently from axin/b-catenin gene mutations. Induction of both endoplasmic reticulum stress and oxidative stress by HCV proteins might also contribute to HCV transformation. Most of the putative transforming functions of the HCV proteins have been defined in artificial cellular systems, which may not be applicable to HCV infection in vivo, and still need to be established in relevant infection and disease models.

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The Hepatitis C Virus Core Protein Interacts with NS5A and Activates Its Caspase-Mediated Proteolytic Cleavage

Cited by 54 publications

References 52 publications

E2 of Hepatitis C Virus Inhibits Apoptosis

E2 of Hepatitis C Virus Inhibits Apoptosis

Diacylglycerol Acyltransferase-1 Localizes Hepatitis C Virus NS5A Protein to Lipid Droplets and Enhances NS5A Interaction with the Viral Capsid Core

Viral hepatitis and liver cancer: the case of hepatitis C

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