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Abstract Details
Genome-wide analysis of host mRNA translation during hepatitis C virus infection
Colman H, Le Berre-Scoul C, Hernandez C, Pierredon S, Bihouée A, Houlgatte R, Vagner S, Rosenberg AR, Féray C. J Virol. 2013 Apr 3. [Epub ahead of print]
Source
Equipe 4271, Université de Nantes.
Abstract
In the model of Huh7.5.1 hepatocyte cells infected by the JFH1 hepatitis C (HCV) strain, transcriptomic and proteomic studies have evidenced modulations of pathways governing mainly apoptosis and cell cycling. Differences between transcriptomic and proteomic studies pointed out to regulations occurring at the post-transcriptional level including the control of mRNA translation. Here, we investigated at the genome-wide level, the translational regulation occurring during HCV infection.Sucrose gradient ultracentrifugation followed by microarray analysis was used to identify translationally-regulated mRNAs (mRNAs associated with ribosomes) from JFH1-infected and uninfected Huh-7.5.1 cells. Translationally regulated mRNAs were found to correspond to genes enriched in specific pathways including vesicular transport and post-transcriptional regulation. Interestingly, the strongest translational regulation was found for mRNAs encoding proteins involved in pre-mRNA splicing, mRNA translation, and protein folding. Strikingly, these pathways were not previously identified, through transcriptomic studies, as being modulated following HCV infection. Importantly, the observed changes in host mRNA translation were directly due to HCV replication rather than to HCV entry since they were not observed in JFH1-infected Huh-7.5.1 cells treated with a potent HCV NS3 protease inhibitor.Overall this study highlights the need to consider, beyond transcriptomic or proteomic studies, the modulation of host mRNA translation as an important aspect of HCV infection.