Virology & Mycology
Open Access

HTLV-1-infected CD4+ T-cells display alternative exon usages that culminate in adult T-cell leukemia

International Conference on Retroviruses & Novel Drugs

June 08-09, 2015 Chicago, USA

Franck Mortreux1, Morgan Thénoz1, Celine Vernin1, Hussein Mortada2, Maroun Karam1, Christiane Pinatel2, Antoine Gessain3, Thomas R Webb4, Didier Auboeuf2 and Eric Wattel1

Posters-Accepted Abstracts: Virol-mycol

Abstract :

Reprogramming cellular gene transcription sustains HTLV-1 viral persistence that ultimately leads to the development of adult T-cell leukemia/lymphoma (ATLL). We hypothesized that besides these quantitative transcriptional effects, HTLV-1 qualitatively modifies the pattern of cellular gene expression. Exon expression analysis shows that patients? untransformed and malignant HTLV-1+ CD4+ T-cells exhibit multiple alternate exon usage (AEU) events. These affect either transcriptionally modified or unmodified genes, culminate in ATLL, and unveil new functional pathways involved in cancer and cell cycle. Unsupervised hierarchical clustering of array data permitted to isolate exon expression patterns of 3977 exons that discriminate uninfected, infected, and transformed CD4+ T-cells. Furthermore, untransformed infected CD4+ clones and ATLL samples shared 486 exon modifications distributed in 320 genes, thereby indicating a role of AEUs in HTLV-1 leukemogenesis. Exposing cells to splicing modulators revealed that Sudemycin E reduces cell viability of HTLV-1 transformed cells without affecting primary control CD4+ cells and HTLV-1 negative cell lines, suggesting that the huge excess of AEU might provide news targets for treating ATLL. Taken together, these data reveal that HTLV-1 significantly modifies the structure of cellular transcripts and unmask new putative leukemogenic pathways and possible therapeutic targets.

Biography :

Franck Mortreux has completed his PhD from Paris 6 University (France) and Postdoctoral studies from Agronomy Universirty of Gembloux (Belgium). He is PI in France in the Ecole Normal Superieur de Lyon (UMR5239, LBMC). His researches are mainly focused on HTLV-1 infection and on molecular mechanisms underlying post-transcriptional modifications, virus persistence and oncogenesis.