Next Article in Journal
Are Circulating Tumor Cells (CTCs) Ready for Clinical Use in Breast Cancer? An Overview of Completed and Ongoing Trials Using CTCs for Clinical Treatment Decisions
Next Article in Special Issue
Mild Iron Overload as Seen in Individuals Homozygous for the Alpha-1 Antitrypsin Pi*Z Variant Does Not Promote Liver Fibrogenesis in HFE Knockout Mice
Previous Article in Journal
Treatment with Human Amniotic Suspension Allograft Improves Tendon Healing in a Rat Model of Collagenase-Induced Tendinopathy
Previous Article in Special Issue
Hepatitis C Virus Enhances the Invasiveness of Hepatocellular Carcinoma via EGFR-Mediated Invadopodia Formation and Activation
Open AccessReview

Hepatitis C Virus Downregulates Core Subunits of Oxidative Phosphorylation, Reminiscent of the Warburg Effect in Cancer Cells

1
Institute of Biochemistry, Medical Faculty, Justus Liebig University, Friedrichstrasse 24, 35392 Giessen, Germany
2
Department of Gastroenterology, Justus Liebig University, Klinikstrasse 33, 35392 Giessen, Germany
3
School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(11), 1410; https://doi.org/10.3390/cells8111410
Received: 16 October 2019 / Revised: 5 November 2019 / Accepted: 6 November 2019 / Published: 8 November 2019
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.
Keywords: HCV; HCC; hepatocellular carcinoma; fibrosis; oxidative phosphorylation; mitochondrial respiratory chain; NADH-ubiquinone oxidoreductase; cytochrome c oxidase; ATP-Synthase; warburg effect HCV; HCC; hepatocellular carcinoma; fibrosis; oxidative phosphorylation; mitochondrial respiratory chain; NADH-ubiquinone oxidoreductase; cytochrome c oxidase; ATP-Synthase; warburg effect
MDPI and ACS Style

Gerresheim, G.K.; Roeb, E.; Michel, A.M.; Niepmann, M. Hepatitis C Virus Downregulates Core Subunits of Oxidative Phosphorylation, Reminiscent of the Warburg Effect in Cancer Cells. Cells 2019, 8, 1410.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop