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

Linda Zane (1) , David Sibon (1, 2) , Lionel Jeannin (1) , Marc Zandecki (3) , Marie-Hélène Delfau-Larue (4) , Antoine Gessain (5) , Olivier Gout (6) , Christiane Pinatel (1) , Agnès Lançon (1) , Franck Mortreux (1) , Eric Wattel (1, 2)

1 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
2 Hôpital Edouard Herriot [CHU - HCL]
3 Laboratoire d'hématologie
4 Laboratoire d'Immunologie
5 Epidémiologie et Physiopathologie des Virus Oncogènes
6 Service de Neurologie

BACKGROUND: 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.

Domains: Microbiology and Parasitology

Linda Zane, David Sibon, Lionel Jeannin, Marc Zandecki, Marie-Hélène Delfau-Larue, et al.. Tax gene expression and cell cycling but not cell death are selected during HTLV-1 infection in vivo.. Retrovirology, 2010, 7, pp.17. ⟨10.1186/1742-4690-7-17⟩. ⟨pasteur-00488306⟩