Hepatitis C Virus downregulates core subunits of oxidative phosphorylation, reminiscent of the warburg effect in cancer cells
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Published version
Date
2019-11-08
Authors
Gerresheim, Gesche K.
Roeb, Elke
Michel, Audrey M.
Niepmann, Michael
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Published Version
Abstract
Hepatitis C Virus (HCV) mainly infects liver hepatocytes and replicates its single-stranded plus strand RNA genome exclusively in the cytoplasm. Viral proteins and RNA interfere with the host cell immune response, allowing the virus to continue replication. Therefore, in about 70% of cases, the viral infection cannot be cleared by the immune system, but a chronic infection is established, often resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Induction of cancer in the host cells can be regarded to provide further advantages for ongoing virus replication. One adaptation in cancer cells is the enhancement of cellular carbohydrate flux in glycolysis with a reduction of the activity of the citric acid cycle and aerobic oxidative phosphorylation. To this end, HCV downregulates the expression of mitochondrial oxidative phosphorylation complex core subunits quite early after infection. This so-called aerobic glycolysis is known as the “Warburg Effect” and serves to provide more anabolic metabolites upstream of the citric acid cycle, such as amino acids, pentoses and NADPH for cancer cell growth. In addition, HCV deregulates signaling pathways like those of TNF-β and MAPK by direct and indirect mechanisms, which can lead to fibrosis and HCC.
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Keywords
HCV , HCC , Hepatocellular carcinoma , Fibrosis , Oxidative phosphorylation , Mitochondrial respiratory chain , NADH-ubiquinone oxidoreductase , Cytochrome c oxidase , ATP-Synthase , Warburg effect
Citation
Gerresheim, G. K., Roeb, E., Michel, A. M. and Niepmann, M. (2019) 'Hepatitis C Virus Downregulates Core Subunits of Oxidative Phosphorylation, Reminiscent of the Warburg Effect in Cancer Cells', Cells, 8(11), 1410. (19pp.) doi: 10.3390/cells8111410