Alternative splicing signatures discriminate ATL cells from untransformed CD4+ counterparts deriving from HTLV-1 infecte
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ORAL PRESENTATION
Open Access
Alternative splicing signatures discriminate ATL cells from untransformed CD4+ counterparts deriving from HTLV-1 infected individuals Morgan Thenoz1*, Céline Vernin1, Christiane Pinatel2, Nicolas Nazaret3, Joel Lachuer3, Antoine Gessain4, Didier Auboeuf5, Eric Wattel1, Franck Mortreux1 From 16th International Conference on Human Retroviruses: HTLV and Related Viruses Montreal, Canada. 26-30 June 2013
The clonal expansion and malignant transformation of HTLV-1 infected CD4+ T-cells have been linked to the reprogramming effects of HTLV-1 on host transcriptional profile. Coupled to transcription, alternative splicing (AS) is a post-transcriptional process that plays critical role in the complexity of transcriptome and splicing abnormalities frequently occur in cancer. To examine whether AS modifications associate with HTLV-1-associated leukemogenesis, we compared the exon expression profiles of ATL cells with that of CD4+ T-cell clones obtained by limited-dilution cloning of PBMC deriving from HTLV-1 carriers. 3 ATL cells and 12 untransformed infected clones clustering in infected, uninfected, PHA-stimulated or unstimulated CD4+ T cells were compared for exon RNA content using Exon Chip Human microarray. Hierarchical clustering analysis identified 12516 alternative spliced events (3642 genes) that clearly separated ATL samples from the 4 untransformed phenotypes mentioned above. In contrast, the exon content of 1539 genes differed between untransformed infected and uninfected T-CD4+ cells. Overall, less than 5% alternatively spliced genes were found differentially expressed at the transcriptional level. Microarray data were confirmed for 18 AS events using exon specific RT-PCR analysis. Pathway analysis of alternatively spliced genes (3642) in ATL cells revealed new AS-based pathways for p53 signaling, cell cycle and DNA replication while those of untransformed infected CD4+ T-cells were enriched in pathways for cellular movement and DNA repair. These findings unveil a new layer of complexity in the interplay between HTLV-1 and host cell gene expression 1 Oncovirologie et Biotherapies, UMR5239 CNRS/ENS Lyon/UCBL/HCL, Hopital Pierre Benite, Lyon, France Full list of author information is available at the end of the article
machinery in which AS might play a central role in tumor initiation and promotion. Authors’ details 1 Oncovirologie et Biotherapies, UMR5239 CNRS/ENS Lyon/UCBL/HCL, Hopital Pierre Benite, Lyon, France. 2Oncovirologie et Biothérapies, Centre Léon Bérard, Lyon, France. 3ProfileXpert, Neurobiotec Service, Bron, France. 4Unit of Epidemiology and Physiopathology of Oncogenic Viruses, Department of Virology, Institut Pasteur, Paris, France. 5Institut National de Santé et de Recherche Médicale U590, Centre Léon Bérard, Lyon, France. Published: 7 January 2014
doi:10.1186/1742-4690-11-S1-O66 Cite this article as: Thenoz et al.: Alternative splicing signatures discriminate ATL cells from untransformed CD4+ counterparts deriving from HTLV-1 infected individuals. Retrovirology
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