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| Status |
Public on Mar 02, 2019 |
| Title |
Cellular gene expression during Hepatitis C Virus replication revealed by Ribosome profiling |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 favours 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 Huh-7.5 hepatoma cells replicating HCV for 6 days.
Results: Established viral replication does not cause global changes in host gene expression - only around 30 genes are differentially expressed. Upregulated genes are related to ER stress, HCV replication and HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, TRIB3) may be subject to uORF mediated translation control in response to stress-induced eIF2 inactivation. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex genes.
Conclusion: After establishing HCV replication, cellular gene expression is reprogrammed towards stress response and HCC development. Downregulation of mitochondrial respiratory chain genes indicates how a virus induces cancer cell-like metabolic reprogramming ("Warburg effect"). Thus, HCV escapes stress response pathways but induces selective gene expression changes which likely are beneficial for chronic infection and cancerogenesis.
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| Overall design |
Transcriptome and translatome changes in Huh-7.5 hepatoma cells replicating HCV for 6 days in comparison to non-infected cells were analyzed, in triplicates, by NGS.
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| Contributor(s) |
Gerresheim GK, Bathke J, Michel AM, Andreev DE, Shalamova LA, Rossbach O, Hu P, Glebe D, Fricke M, Marz M, Goesmann A, Kiniry SJ, Baranov P, Shatsky IN, Niepmann M |
| Citation(s) |
30875926 |
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| Submission date |
Mar 01, 2019 |
| Last update date |
Mar 02, 2021 |
| Contact name |
Audrey M Michel |
| E-mail(s) |
A.Michel@ucc.ie
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| Phone |
+353 876217126
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| Organization name |
University College Cork
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| Department |
School of Biochemistry and Cell Biology
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| Lab |
Baranov
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| Street address |
Western Gateway, Western Road
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| City |
Cork |
| State/province |
Cork |
| ZIP/Postal code |
T12 XF62 |
| Country |
Ireland |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA525090 |
| SRA |
SRP187206 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE127713_Gerresheim_et_al_2019_IJMS_RNAseq_HCV_vs_mock.xlsx |
7.9 Mb |
(ftp)(http) |
XLSX |
| GSE127713_Gerresheim_et_al_2019_IJMS_Riboseq_HCV_vs_mock.xlsx |
9.4 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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