Hepatitis C virus, mitochondria and auto/mitophagy: Exploiting a host defense mechanism

Ruggieri, Vitalba

doi:10.3748/wjg.v20.i10.2624

Cited by 15 publications

(8 citation statements)

References 77 publications

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“…In the case of HCV, viral proteins are enriched on mitochondria and MAMs, and viral infection promotes mitochondrial fragmentation and mitophagy 118,154,155 (FIG. 4).…”

Section: Mitochondriamentioning

confidence: 99%

Rewiring cellular networks by members of the Flaviviridae family

et al. 2018

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Members of the Flaviviridae virus family comprise a large group of enveloped viruses with a single-strand RNA genome of positive polarity. Several genera belong to this family, including the Hepacivirus genus, of which hepatitis C virus (HCV) is the prototype member, and the Flavivirus genus, which contains both dengue virus and Zika virus. Viruses of these genera differ in many respects, such as the mode of transmission or the course of infection, which is either predominantly persistent in the case of HCV or acutely self-limiting in the case of flaviviruses. Although the fundamental replication strategy of Flaviviridae members is similar, during the past few years, important differences have been discovered, including the way in which these viruses exploit cellular resources to facilitate viral propagation. These differences might be responsible, at least in part, for the various biological properties of these viruses, thus offering the possibility to learn from comparisons. In this Review, we discuss the current understanding of how Flaviviridae viruses manipulate and usurp cellular pathways in infected cells. Specifically, we focus on comparing strategies employed by flaviviruses with those employed by hepaciviruses, and we discuss the importance of these interactions in the context of viral replication and antiviral therapies.

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“…In the case of HCV, viral proteins are enriched on mitochondria and MAMs, and viral infection promotes mitochondrial fragmentation and mitophagy 118,154,155 (FIG. 4).…”

Section: Mitochondriamentioning

confidence: 99%

Rewiring cellular networks by members of the Flaviviridae family

et al. 2018

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“…Evidence suggests that mitophagy may counteract apoptosis [ 13 – 15 ]. Several viruses such as Hepatitis B Virus (HBV) [ 16 ] and Hepatitis C Virus (HCV) [ 17 ] stimulate mitophagy and attenuate apoptosis, presumably to enhance viral replication. Although TGEV induces apoptosis in some cell lines, but not in intestinal epithelial cells [ 5 ], the potential role played by mitophagy in this system has not yet been explored.…”

Section: Introductionmentioning

confidence: 99%

Mitophagy in TGEV infection counteracts oxidative stress and apoptosis

et al. 2016

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The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection.

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“…A recently emerged property of HCV is the enhanced mitophagy in the host cell (Kim et al, 2013 , 2014 ; Ruggieri et al, 2014 ). Mitophagy is a selective autophagic degradation of mitochondria which is part of a quality control processing of the cell (Anding and Baehrecke, 2017 ).…”

Section: Inhibitors Of the Er And Mitochondrial Ca 2+ mentioning

confidence: 99%

Targeting Endoplasmic Reticulum and/or Mitochondrial Ca2+ Fluxes as Therapeutic Strategy for HCV Infection

et al. 2018

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Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions 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 also localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory and need to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems. In the past decade we have been proposing a temporal sequence of events in the HCV-infected cell whereby the primary alteration is localized at the mitochondria-associated ER membranes and causes release of Ca2+ from the ER, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen and nitrogen species and a progressive metabolic adaptive response consisting in decreased oxidative phosphorylation and enhanced aerobic glycolysis and lipogenesis. Here we resume the major results provided by our group in the context of HCV-mediated alterations of the cellular inter-compartmental calcium flux homeostasis and present new evidence suggesting targeting of ER and/or mitochondrial calcium transporters as a novel therapeutic strategy.

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Hepatitis C virus, mitochondria and auto/mitophagy: Exploiting a host defense mechanism

Cited by 15 publications

References 77 publications

Rewiring cellular networks by members of the Flaviviridae family

Rewiring cellular networks by members of the Flaviviridae family

Mitophagy in TGEV infection counteracts oxidative stress and apoptosis

Targeting Endoplasmic Reticulum and/or Mitochondrial Ca2+ Fluxes as Therapeutic Strategy for HCV Infection

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