title: Genome-wide analysis of host mRNA translation during hepatitis C virus infection.
abstract: In the model of Huh-7.5.1 hepatocyte cells infected by the JFH1 hepatitis C virus (HCV) strain, transcriptomic and proteomic studies have revealed modulations of pathways governing mainly apoptosis and cell cycling. Differences between transcriptomic and proteomic studies pointed to regulations occurring at the posttranscriptional level, including the control of mRNA translation. In this study, 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 posttranscriptional 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.
authors.affiliation: Equipe 4271, Université de Nantes, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Colman
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Berre-Scoul
authors.forename: Céline
authors.initials: C
authors.lastname: Hernandez
authors.forename: Sandra
authors.initials: S
authors.lastname: Pierredon
authors.forename: Audrey
authors.initials: A
authors.lastname: Bihouée
authors.forename: Rémi
authors.initials: R
authors.lastname: Houlgatte
authors.forename: Stephan
authors.initials: S
authors.lastname: Vagner
authors.forename: Arielle R
authors.initials: AR
authors.lastname: Rosenberg
authors.forename: Cyrille
authors.initials: C
authors.lastname: Féray
mesh_terms: D045744:Cell Line, Tumor; D002499:Centrifugation, Density Gradient; D016678:Genome; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006526:Hepatitis C / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D012333:RNA, Messenger
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