Involvement of mitochondrial permeability transition in hepatitis B virus replication

Tan, Chang; Guo, Hua; Zheng, Maofa; Chen, Yu; Huang, Weida

doi:10.1016/j.virusres.2009.08.001

Cited by 22 publications

(16 citation statements)

References 25 publications

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“…Some pathogens interact with a variety of mitochondrial components to modulate MMP for their own benefit (1). For example, the influenza virus protein PB1-F2 and the hepatitis B virus X protein both induce MMP during the infection process (28,41), whereas the vaccinia virus protein F1L inhibits both MMP and the release of cytochrome c (9). Our present data suggest that WSSV infection also interferes with mitochondrial activity: Fig.…”

Section: Discussionmentioning

confidence: 48%

White Spot Syndrome Virus Induces Metabolic Changes Resembling the Warburg Effect in Shrimp Hemocytes in the Early Stage of Infection

Chen

Aoki

Huang

et al. 2011

J Virol

170

147

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The Warburg effect is an abnormal glycolysis response that is associated with cancer cells. Here we present evidence that metabolic changes resembling the Warburg effect are induced by a nonmammalian virus. When shrimp were infected with white spot syndrome virus (WSSV), changes were induced in several metabolic pathways related to the mitochondria. At the viral genome replication stage (12 h postinfection [hpi]), glucose consumption and plasma lactate concentration were both increased in WSSV-infected shrimp, and the key enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PDH), showed increased activity. We also found that at 12 hpi there was no alteration in the ADP/ATP ratio and that oxidative stress was lower than that in uninfected controls. All of these results are characteristic of the Warburg effect as it is present in mammals. There was also a significant decrease in triglyceride concentration starting at 12 hpi. At the late stage of the infection cycle (24 hpi), hemocytes of WSSV-infected shrimp showed several changes associated with cell death. These included the induction of mitochondrial membrane permeabilization (MMP), increased oxidative stress, decreased glucose consumption, and disrupted energy production. A previous study showed that WSSV infection led to upregulation of the voltage-dependent anion channel (VDAC), which is known to be involved in both the Warburg effect and MMP. Here we show that double-stranded RNA (dsRNA) silencing of the VDAC reduces WSSV-induced mortality and virion copy number. For these results, we hypothesize a model depicting the metabolic changes in host cells at the early and late stages of WSSV infection.During the early stage of most lytic viral infections, when the virus genome is being replicated, viral products will modulate host cell metabolic homeostasis to boost activities such as glycolysis, the pentose phosphate pathway (PPP), and fatty acid metabolism in order to favor pathogen biosynthesis and fulfill the pathogen's energy requirements. Subsequently, at the late stage of infection, when virion maturation is complete, damage to the cell's metabolism can lead to cell death, which in turn allows the new virions to be released. Using cell culture systems and state-of-the-art techniques, systems-level metabolic flux profilings have monitored these events in several mammalian viruses, including human cytomegalovirus (HCMV) and hepatitis C virus (HCV) (6,20,21). In some viruses, such as HCV and Kaposi's sarcoma herpesvirus (KSHV), these metabolic changes are characteristic of the Warburg effect (5, 6). The Warburg effect, which is an abnormal glycolytic response that is associated with cancer cells and tumors, involves the mitochondria and is partly mediated by the voltage-dependent anion channel (VDAC) (19). Interestingly, the VDAC also plays a critical role in cell death via its involvement in mitochondrial membrane permeabilization (MMP) (27,30).In a global study of the changes in protein expression levels in the stomachs of shrimp in...

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Section: Discussionmentioning

confidence: 48%

White Spot Syndrome Virus Induces Metabolic Changes Resembling the Warburg Effect in Shrimp Hemocytes in the Early Stage of Infection

Chen

Aoki

Huang

et al. 2011

J Virol

170

147

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“…HBx exerts powerful effects on mitochondria, either directly through their channel-forming activity or indirectly through associations with endogenous channels [108][109][110]. Two mitochondrial proteins, heat-shock proteins 60 and 70 [111,112], as well as the VDAC isoform, VDAC3 [113], have also been identified as cellular targets of HBx.…”

Section: Hbx and Regulation Of Apoptosismentioning

confidence: 99%

Hepatitis B virus X gene and hepatocarcinogenesis

2011

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Chronic hepatitis B virus (HBV) infection has been identified as a major risk factor in hepatocellular carcinoma (HCC), which is one of the most common cancers worldwide. The pathogenesis of HBV-mediated hepatocarcinogenesis is, however, incompletely understood. Evidence suggests that the HBV X protein (HBx) plays a crucial role in HCC development. HBx is a multifunctional regulator that modulates transcription, signal transduction, cell cycle progression, apoptosis, protein degradation pathways, and genetic stability through interaction with host factors. This review describes the current state of knowledge of the molecular pathogenesis of HBV-induced HCC, with a focus on the role of HBx in hepatocarcinogenesis.

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“…Mitochondrial Ca 2+ overload, ROS overproduction and decreased ATP synthesis in chronic HCV infection may trigger mPTP opening, with resulting mitochondrial swelling and cell death [53]. Moreover, the non-structural X protein of HBV may induce mPTP opening and Ca 2+ effusion during viral replication [105]. Hydrophobic bile acids and bile salts cause mPTP opening [106].…”

Section: Mitochondrial Uncoupling and Cell Deathmentioning

confidence: 99%

Targeting Mitochondria: A New Promising Approach for the Treatment of Liver Diseases

Serviddio

Bellanti

Sastre

et al. 2010

CMC

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Mitochondrial dysfunction acts as a common pathogenetic mechanism in several acute and chronic liver diseases, such as Alcoholic and Non-Alcoholic Fatty Liver Disease (NAFLD), drug-induced steatohepatitis, viral hepatitis, biliary cirrhosis, hepatocellular carcinoma, ischemia/reperfusion injury and transplant rejection. In particular mitochondrial uncoupling,has been recently identified to play a determinant role in the pathogenesis of liver diseases by causing decrease of mitochondrial proton motive force and ATP depletion. Damaged mitochondria present defects in lipid homeostasis, bioenergetics impairment and overproduction of Reactive Oxygen Species (ROS), leading to lipid accumulation and oxidative stress. Dysfunctional and/or uncoupled mitochondria enhance the susceptibility of hepatocytes to cell death by necrosis, via ATP depletion, or by apoptosis, via membrane permeabilization. Thus, prevention of mitochondrial alterations promises to be an effective strategy for treatment of liver diseases. However, no therapy has proven to be absolutely effective, whereas those that are beneficial present several side effects. The present review summarizes the recent approaches in mitochondrial drug deliver systems and focuses on mitochondria-targeted molecules application in liver disease. New selective molecules and nanocarriers technology are also considered as potentially effective in the targeting of mitochondrial dysfunction in liver pathology.

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Involvement of mitochondrial permeability transition in hepatitis B virus replication

Cited by 22 publications

References 25 publications

White Spot Syndrome Virus Induces Metabolic Changes Resembling the Warburg Effect in Shrimp Hemocytes in the Early Stage of Infection

White Spot Syndrome Virus Induces Metabolic Changes Resembling the Warburg Effect in Shrimp Hemocytes in the Early Stage of Infection

Hepatitis B virus X gene and hepatocarcinogenesis

Targeting Mitochondria: A New Promising Approach for the Treatment of Liver Diseases

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