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You are here: Home / Teams / Regulation of Genome Architecture and Dynamics of Splicing (ReGArDS) - D. Auboeuf and C. Bourgeois / Publications / Tax gene expression and cell cycling but not cell death are selected during HTLV-1 infection in vivo.

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

Linda Zane, David Sibon, Lionel Jeannin, Marc Zandecki, Marie-Helene Delfau-Larue, Antoine Gessain, Olivier Gout, Christiane Pinatel, Agnes Lancon, Franck Mortreux, and Eric Wattel (2010)

Retrovirology, 7:17.

BACKGROUND: Adult T cell leukemia results from the malignant transformation of aCD4+ 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 thoseobserved in cloned T cells from patients infected for >6-26 years, we found thatin 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.

 
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