HCV NS4B induces apoptosis through the mitochondrial death pathway

Zhao, Peng; Han, Tao; Guo, Jin-Jing; Zhu, Shengli; Wang, Jun; Ao, Fang; Jing, Ming-Zhen; She, Yuanbin; Wu, Zhao; Ye, Linbai

doi:10.1016/j.virusres.2012.04.006

Cited by 24 publications

(22 citation statements)

References 45 publications

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“…The effector caspases are activated by the active initiator caspases. In particular, the most widely studied member of caspase family is caspase-3 which is partially or totally responsible for the proteolytic cleavage of several proteins such as PARP and the activation of death events such as DNA single-stran d breakage (Cohen, 1997;Ko et al, 2009;Zhao et al, 2012 ). An in vitro study has reported that sulfites react with cytosine and uracil in DNA and RNA respectively and damage DNA chains presumabl y by a free radical mechanism (Shi and Mao, 1994).…”

Section: Discussionmentioning

confidence: 99%

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Ghrelin inhibits sodium metabisulfite induced oxidative stress and apoptosis in rat gastric mucosa

Ercan

Basaranlar

Gungor

et al. 2013

Food and Chemical Toxicology

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Section: Discussionmentioning

confidence: 99%

“…Cytochrome c induces the formation of the apoptoso me complex, that recruits and activates procaspase 9. Activated caspase 9 cleaves and activates caspase 3 which in turn activates downstre am death events such as DNA single-stran d breakage and poly (ADP-ribose) polymerase (PARP) cleavage (Zhao et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Ghrelin inhibits sodium metabisulfite induced oxidative stress and apoptosis in rat gastric mucosa

Ercan

Basaranlar

Gungor

et al. 2013

Food and Chemical Toxicology

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“…HCV NS5A stabilizes PARP-1 by blocking caspase 3 mediated-cleavage (Zemel et al, 2011). PARP-1 cleavage is also accelerated by HCV (Zhao et al, 2012). The latter may permit the propagation of mutations and promote genetic instability in HCV infected cells.…”

Section: Hepatitis B Virus (Hbv) and Hepatitis C Virus (Hcv): Direct mentioning

confidence: 99%

Human Viral Oncogenesis: A Cancer Hallmarks Analysis

Mesri

Feitelson

Münger

2014

Cell Host & Microbe

547

555

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Approximately twelve percent of all human cancers are caused by oncoviruses. Human viral oncogenesis is complex and only a small percentage of the infected individuals develop cancer and often many years to decades after initial infection. This reflects the multistep nature of viral oncogenesis, host genetic variability and the fact that viruses contribute to only a portion of the oncogenic events. In this review, the Hallmarks of Cancer framework of Hanahan & Weinberg (2000 and 2011) is used to dissect the viral, host and environmental co-factors that contribute to the biology of multistep oncogenesis mediated by established human oncoviruses. The viruses discussed include Epstein Barr Virus (EBV), high-risk Human Papillomaviruses (HPV16/18), Hepatitis B and C viruses (HBV, HCV respectively), Human T-cell lymphotropic virus-1 (HTLV-1) and Kaposi’s sarcoma herpesvirus (KSHV).

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“…NS4A expression in Huh7 cells induces cell death, decreases Δψm, induces cytochrome c release and caspase 3, but not caspase 8, activation, strongly suggesting that NS4A induces apoptosis through the mitochondria-mediated pathway [47]. NS4B was also found to induce apoptosis via the mitochondrial death pathway in Huh7 cells, where it induced cytochrome c release and Δψm decrease, coupled with caspase 3, 7 and 9 activation and PARP cleavage [141]; however, in U-2 OS cells, its action was caspase-independent [134]. NS5A has been shown to inhibit apoptosis by induction of survivin expression, an inhibitor of caspases [142], by blocking cytochrome c release [143], by the sequestration of p53 in the cytoplasm to prevent pro-apoptotic gene transcription [144] and by activation of the PKB/Akt and NFkB signaling pathways [96,145].…”

Section: Mitochondrial Functions Altered By Hcv Infectionmentioning

confidence: 99%

Hepatitis C Virus-Induced Mitochondrial Dysfunctions

Brault

Lévy

Bartosch

2013

Viruses

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Chronic hepatitis C is characterized by metabolic disorders and a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that lead in the long term to hepatocellular carcinoma. Many lines of evidence suggest that mitochondrial dysfunctions, including modification of metabolic fluxes, generation and elimination of oxidative stress, Ca2+ signaling and apoptosis, play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV) proteins localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory, probably due to the use of artificial expression and replication systems. In vivo studies are hampered by the fact that innate and adaptive immune responses will overlay mitochondrial dysfunctions induced directly in the hepatocyte by HCV. Thus, the molecular aspects underlying HCV-induced mitochondrial dysfunctions and their roles in viral replication and the associated pathology need yet to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems.

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HCV NS4B induces apoptosis through the mitochondrial death pathway

Cited by 24 publications

References 45 publications

Ghrelin inhibits sodium metabisulfite induced oxidative stress and apoptosis in rat gastric mucosa

Ghrelin inhibits sodium metabisulfite induced oxidative stress and apoptosis in rat gastric mucosa

Human Viral Oncogenesis: A Cancer Hallmarks Analysis

Hepatitis C Virus-Induced Mitochondrial Dysfunctions

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