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.
1.Justus Liebig Univ, Fac Med, Inst Biochem, Friedrichstr 24, D-35392 Giessen, Germany 2.Justus Liebig Univ, Fac Biol & Chem, Bioinformat & Syst Biol, D-35392 Giessen, Germany 3.Univ Coll Cork, Sch Biochem & Cell Biol, Cork T12 XF62, Ireland 4.Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow 119234, Russia 5.Justus Liebig Univ, Fac Vet Med, Inst Virol, D-356392 Giessen, Germany 6.Justus Liebig Univ, Fac Biol & Chem, Inst Biochem, D-35392 Giessen, Germany 7.Justus Liebig Univ, Inst Med Virol, Natl Reference Ctr Hepatitis B&D Viruses, Giessen, Germany 8.German Ctr Infect Res DZIF, Partner Site Giessen, D-35392 Giessen, Germany 9.Genevention GmbH, D-37079 Gottingen, Germany 10.Friedrich Schiller Univ Jena, Fac Math & Comp Sci, RNA Bioinformat & High Throughput Anal, D-07743 Jena, Germany
Recommended Citation:
Gerresheim, Gesche K.,Bathke, Jochen,Michel, Audrey M.,et al. Cellular Gene Expression during Hepatitis C Virus Replication as Revealed by Ribosome Profiling[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2019-01-01,20(6)