Cellular Gene Expression during Hepatitis C Virus Replication as Revealed by Ribosome Profiling.
Carcinoma, Hepatocellular
/ genetics
Cell Line, Tumor
Endoplasmic Reticulum Stress
Gene Expression Regulation, Neoplastic
Hepacivirus
/ pathogenicity
Hepatitis C
/ genetics
Humans
Liver Neoplasms
/ genetics
Models, Biological
Open Reading Frames
Oxidative Phosphorylation
Ribosomes
/ genetics
Virus Replication
ER stress
HCC
HCV
Riboseq
Warburg effect
hepatocellular carcinoma
liver cancer
mitochondria
respiratory chain
ribosome profiling
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
31
01
2019
revised:
06
03
2019
accepted:
12
03
2019
entrez:
17
3
2019
pubmed:
17
3
2019
medline:
4
7
2019
Statut:
epublish
Résumé
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. We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in the Huh-7.5 hepatocarcinoma cell line replicating HCV for 6 days. 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 ( 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.
Sections du résumé
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 (
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.
Identifiants
pubmed: 30875926
pii: ijms20061321
doi: 10.3390/ijms20061321
pmc: PMC6470931
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 197785619 SFB 1021
Pays : International
Organisme : Land Hessen
ID : Medical RNomics
Pays : International
Organisme : Wellcome Trust
ID : 210692/Z/18/Z
Pays : United Kingdom
Organisme : Deutsche Forschungsgemeinschaft
ID : MA 5082/7-1
Pays : International
Organisme : Russian Science Foundation
ID : 16-14-10065
Pays : International
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