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

Abstract

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 theexpression 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. © 2010 Zane et al; licensee BioMed Central Ltd.