Cloned HTLV-1+CD4+, but not CD8+, T-cells display an oncogenic miRNome

HTLV-1 persistence in vivo relies on the persistent clonal expansion of its host cells. These are CD4+ and CD8+ T cells, yet ATL is regularly CD4+. Accordingly, untransformed HTLV-1+CD4+ but not CD8+ T cells cloned from carriers cumulate the features of preleukemic cells, including multinuclearity, chromatin bridges, increased cell cycling and inappropriate telomerase activity. MicroRNAs (miR) modify the maturation of a plethora of T-cells RNA and their deregulation would therefore constitute an appropriate explanation for the Tax-dependent or -independent pleiotropic changes in the phenotype of HTLV-1+CD4+ T cells. As the miRNome of naturally infected untransformed cells has not been investigated to date, we assessed the miR expression profiling of T cells cloned from carriers. Microarray results, confirmed by quantitative RTPCR, showed that, upon infection, CD4+ and CD8+ clones yielded aberrant expression of 15 distinct miRs including miR-34b and miR-494 that were respectively over- and underexpressed in both compartments. The more prominent effect of the infection consisted in the CD4+-restricted overexpression of the cancer-related miRs miR-21, -27b and -23b associated with the CD4+-restricted downregulation of the proapoptotic miR-15 and -16. Data were extended by the analysis of 40 additional CD4+ clones (20 infected). Crossing the miRNome against the whole transcriptome data identified putative miR-targeted genes. In silico, those targeted by miR-23b and -27b defined 2 hitherto unknown pathways involving the cell cycle and genetic disorders. Therefore HTLV-1 triggers a phenotype-specific miR signature consistent with the preleukemic HTLV-1+CD4+ phenoty

A propos de l'Hercule Farnèse de Jean Cornu dans le jardin du château de Versailles

Pinatel Christiane. A propos de l'Hercule Farnèse de Jean Cornu dans le jardin du château de Versailles. In: Versalia. Revue de la Société des Amis de Versailles, n°3, 2000. pp. 140-152

De quelques modèles de l’art grec dessinés dans sa jeunesse par Ingres

Pinatel Christiane. De quelques modèles de l’art grec dessinés dans sa jeunesse par Ingres. In: Bulletin de la Société Nationale des Antiquaires de France, 2008, 2015. pp. 203-205

La formation de la collection de moulages d'après l'antique à Versailles.

Pinatel Christiane. La formation de la collection de moulages d'après l'antique à Versailles. In: Bulletin de la Société Nationale des Antiquaires de France, 1996, 1999. pp. 318-327

HTLV-1 bZIP Factor HBZ Promotes Cell Proliferation and Genetic Instability by Activating OncomiRs

International audienc

Tax gene expression and cell cycling but not cell death are selected during HTLV-1 infection in vivo.

International audienceBACKGROUND: Adult T cell leukemia results from the malignant transformation of a CD4+ lymphoid clone carrying an integrated HTLV-1 provirus that has undergone several oncogenic events over a 30-60 year period of persistent clonal expansion. Both CD4+ and CD8+ lymphocytes are infected in vivo; their expansion relies on CD4+ cell cycling and on the prevention of CD8+ cell death. Cloned infected CD4+ but not CD8+ T cells from patients without malignancy also add up nuclear and mitotic defects typical of genetic instability related to the expression of the virus-encoded oncogene tax. HTLV-1 expression is cancer-prone in vitro, but in vivo numerous selection forces act to maintain T cell homeostasis and are possibly involved in clonal selection. RESULTS: Here we demonstrate that the HTLV-1 associated CD4+ preleukemic phenotype and the specific patterns of CD4+ and CD8+ clonal expansion are in vivo selected processes. By comparing the effects of recent (1 month) experimental infections performed in vitro and those observed in cloned T cells from patients infected for >6-26 years, we found that in chronically HTLV-1 infected individuals, HTLV-1 positive clones are selected for tax expression. In vivo, infected CD4+ cells are positively selected for cell cycling whereas infected CD8+ cells and uninfected CD4+ cells are negatively selected for the same processes. In contrast, the known HTLV-1-dependent prevention of CD8+ T cell death pertains to both in vivo and in vitro infected cells. CONCLUSIONS: Therefore, virus-cell interactions alone are not sufficient to initiate early leukemogenesis in vivo