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Cellular Gene Expression during Hepatitis C Virus Replication as Revealed by Ribosome Profiling

Gerresheim, Gesche K. ; Bathke, Jochen ; Michel, Audrey M. ; Andreev, Dmitri E. ; Shalamova, Lyudmila A. ; Rossbach, Oliver ; Hu, Pan ; Glebe, Dieter ; Fricke, Markus ; Marz, Manja ; Goesmann, Alexander ; Kiniry, Stephen J. ; Baranov, Pavel V. ; Shatsky, Ivan N. ; Niepmann, Michael


Originalveröffentlichung: (2019) International Journal of Molecular Sciences 20(6):1321 doi: 10.3390/ijms20061321
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URN: urn:nbn:de:hebis:26-opus-157390
URL: http://geb.uni-giessen.de/geb/volltexte/2020/15739/


Freie Schlagwörter (Englisch): HCV , HCC , hepatocellular carcinoma , liver cancer , Warburg effect
Sammlung: Open Access - Publikationsfonds
Universität Justus-Liebig-Universit√§t Gie√üen
Institut: Institute of Biochemistry
Fachgebiet: Medizin
DDC-Sachgruppe: Medizin
Dokumentart: Aufsatz
Sprache: Englisch
Erstellungsjahr: 2019
Publikationsdatum: 01.12.2020
Kurzfassung auf Englisch: 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.
Lizenz: Lizenz-Logo  Creative Commons - Namensnennung 4.0