Cellular gene expression during Hepatitis C virus replication as revealed by Ribosome Profiling

dc.contributor.authorGerresheim, Gesche K.
dc.contributor.authorBathke, Jochen
dc.contributor.authorMichel, Audrey M.
dc.contributor.authorAndreev, Dmitry E.
dc.contributor.authorShalamova, Lyudmila A.
dc.contributor.authorRossbach, Oliver
dc.contributor.authorHu, Pan
dc.contributor.authorGlebe, Dieter
dc.contributor.authorFricke, Markus
dc.contributor.authorMarz, Manja
dc.contributor.authorGoesmann, Alexander
dc.contributor.authorKiniry, Stephen J.
dc.contributor.authorBaranov, Pavel V.
dc.contributor.authorShatsky, Ivan N.
dc.contributor.authorNiepmann, Michael
dc.contributor.funderDeutsche Forschungsgemeinschaften
dc.contributor.funderIrish Research Councilen
dc.contributor.funderRussian Science Foundationen
dc.contributor.funderMedical RNomicsen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderWellcome Trusten
dc.date.accessioned2019-11-19T10:09:28Z
dc.date.available2019-11-19T10:09:28Z
dc.date.issued2019-03-15
dc.description.abstractBackground: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favors HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known. Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in the Huh-7.5 hepatocarcinoma cell line replicating HCV for 6 days. Results: Established viral replication does not cause global changes in host gene expression—only around 30 genes are significantly differentially expressed. Upregulated genes are related to ER stress and HCV replication, and several regulated genes are known to be involved in HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, and TRIB3) may be subject to upstream open reading frame (uORF) mediated translation control. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex core subunit genes. Conclusion: After establishing HCV replication, the lack of global changes in cellular gene expression indicates an adaptation to chronic infection, while the downregulation of mitochondrial respiratory chain genes indicates how a virus may further contribute to cancer cell-like metabolic reprogramming (“Warburg effect”) even in the hepatocellular carcinoma cells used here.en
dc.description.sponsorship210692/Z/18/Z; 197785619—SFB 1021; 16-14-10065; Land Hessen LOEWE granten
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid1321en
dc.identifier.citationGerresheim, G.K., Bathke, J., Michel, A.M., Andreev, D.E., Shalamova, L.A., Rossbach, O., Hu, P., Glebe, D., Fricke, M., Marz, M. and Goesmann, A., 2019. Cellular Gene Expression during Hepatitis C Virus Replication as Revealed by Ribosome Profiling. International journal of molecular sciences, 20(6), (1321). DOI:10.3390/ijms20061321en
dc.identifier.doi10.3390/ijms20061321en
dc.identifier.eissn1422-0067
dc.identifier.endpage19en
dc.identifier.issn1661-6596
dc.identifier.issued6en
dc.identifier.journaltitleInternational Journal of Molecular Sciencesen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9038
dc.identifier.volume20en
dc.language.isoenen
dc.publisherMDPIen
dc.relation.urihttps://www.mdpi.com/1422-0067/20/6/1321
dc.rights© 2019 by the authors. Licensee MDPI, Basel, Switzerlanden
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectHCVen
dc.subjectHCCen
dc.subjectHepatocellular carcinomaen
dc.subjectLiver canceren
dc.subjectWarburg effecten
dc.subjectER stressen
dc.subjectRibosome profilingen
dc.subjectRiboseqen
dc.subjectRespiratory chainen
dc.subjectMitochondriaen
dc.titleCellular gene expression during Hepatitis C virus replication as revealed by Ribosome Profilingen
dc.typeArticle (peer-reviewed)en
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