Hepatitis C Virus downregulates core subunits of oxidative phosphorylation, reminiscent of the warburg effect in cancer cells

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dc.contributor.authorGerresheim, Gesche K.
dc.contributor.authorRoeb, Elke
dc.contributor.authorMichel, Audrey M.
dc.contributor.authorNiepmann, Michael
dc.contributor.funderDeutsche Forschungsgemeinschaften
dc.contributor.funderIrish Research Councilen
dc.date.accessioned2019-12-05T10:22:26Z
dc.date.available2019-12-05T10:22:26Z
dc.date.issued2019-11-08
dc.description.abstractHepatitis 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.en
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (Project Number 197785619)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid1410en
dc.identifier.citationGerresheim, 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/cells8111410en
dc.identifier.doi10.3390/cells8111410en
dc.identifier.eissn2073-4409
dc.identifier.endpage19en
dc.identifier.issued11en
dc.identifier.journaltitleCellsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9336
dc.identifier.volume8en
dc.language.isoenen
dc.publisherMDPIen
dc.rights©2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectHCVen
dc.subjectHCCen
dc.subjectHepatocellular carcinomaen
dc.subjectFibrosisen
dc.subjectOxidative phosphorylationen
dc.subjectMitochondrial respiratory chainen
dc.subjectNADH-ubiquinone oxidoreductaseen
dc.subjectCytochrome c oxidaseen
dc.subjectATP-Synthaseen
dc.subjectWarburg effecten
dc.titleHepatitis C Virus downregulates core subunits of oxidative phosphorylation, reminiscent of the warburg effect in cancer cellsen
dc.typeArticle (peer-reviewed)en
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