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  • Oral presentation
  • Open Access

Alternative splicing signatures discriminate ATL cells from untransformed CD4+ counterparts deriving from HTLV-1 infected individuals

  • 1,
  • 1,
  • 2,
  • 3,
  • 3,
  • 4,
  • 5,
  • 1 and
  • 1
Retrovirology201411 (Suppl 1) :O66

https://doi.org/10.1186/1742-4690-11-S1-O66

  • Published:

Keywords

  • Alternative Splice
  • Exon Expression
  • Infected Clone
  • Clone Cluster
  • Host Cell Gene

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 machinery in which AS might play a central role in tumor initiation and promotion.

Authors’ Affiliations

(1)
Oncovirologie et Biotherapies, UMR5239 CNRS/ENS Lyon/UCBL/HCL, Hopital Pierre Benite, Lyon, France
(2)
Oncovirologie et Biothérapies, Centre Léon Bérard, Lyon, France
(3)
ProfileXpert, Neurobiotec Service, Bron, France
(4)
Unit of Epidemiology and Physiopathology of Oncogenic Viruses, Department of Virology, Institut Pasteur, Paris, France
(5)
Institut National de Santé et de Recherche Médicale U590, Centre Léon Bérard, Lyon, France

Copyright

© Thenoz et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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