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

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dc.contributor.author Gerresheim, Gesche K.
dc.contributor.author Bathke, Jochen
dc.contributor.author Michel, Audrey M.
dc.contributor.author Andreev, Dmitri E.
dc.contributor.author Shalamova, Lyudmila A.
dc.contributor.author Rossbach, Oliver
dc.contributor.author Hu, Pan
dc.contributor.author Glebe, Dieter
dc.contributor.author Fricke, Markus
dc.contributor.author Marz, Manja
dc.contributor.author Goesmann, Alexander
dc.contributor.author Kiniry, Stephen J.
dc.contributor.author Baranov, Pavel V.
dc.contributor.author Shatsky, Ivan N.
dc.contributor.author Niepmann, Michael
dc.date.accessioned 2019-11-19T10:09:28Z
dc.date.available 2019-11-19T10:09:28Z
dc.date.issued 2019-03-15
dc.identifier.citation Gerresheim, 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/ijms20061321 en
dc.identifier.volume 20 en
dc.identifier.issued 6 en
dc.identifier.startpage 1 en
dc.identifier.endpage 19 en
dc.identifier.issn 1661-6596
dc.identifier.uri http://hdl.handle.net/10468/9038
dc.identifier.doi 10.3390/ijms20061321 en
dc.description.abstract Background: 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.sponsorship 210692/Z/18/Z; 197785619—SFB 1021; 16-14-10065; Land Hessen LOEWE grant en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher MDPI en
dc.relation.uri https://www.mdpi.com/1422-0067/20/6/1321
dc.rights © 2019 by the authors. Licensee MDPI, Basel, Switzerland en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject HCV en
dc.subject HCC en
dc.subject Hepatocellular carcinoma en
dc.subject Liver cancer en
dc.subject Warburg effect en
dc.subject ER stress en
dc.subject Ribosome profiling en
dc.subject Riboseq en
dc.subject Respiratory chain en
dc.subject Mitochondria en
dc.title Cellular gene expression during Hepatitis C virus replication as revealed by Ribosome Profiling en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Pavel Baranov, School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: p.baranov@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Deutsche Forschungsgemeinschaft en
dc.contributor.funder Irish Research Council en
dc.contributor.funder Russian Science Foundation en
dc.contributor.funder Medical RNomics en
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Health Research Board en
dc.contributor.funder Wellcome Trust en
dc.description.status Peer reviewed en
dc.identifier.journaltitle International Journal of Molecular Sciences en
dc.internal.IRISemailaddress p.baranov@ucc.ie en
dc.identifier.articleid 1321 en
dc.identifier.eissn 1422-0067

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© 2019 by the authors. Licensee MDPI, Basel, Switzerland Except where otherwise noted, this item's license is described as © 2019 by the authors. Licensee MDPI, Basel, Switzerland
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