Email updates

Keep up to date with the latest news and content from Retrovirology and BioMed Central.

Open Access Highly Accessed Research

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

Linda Zane1, David Sibon127, Lionel Jeannin1, Marc Zandecki3, Marie-Hélène Delfau-Larue4, Antoine Gessain5, Olivier Gout6, Christiane Pinatel1, Agnès Lançon1, Franck Mortreux1 and Eric Wattel12*

Author Affiliations

1 CNRS UMR5239, Université de Lyon, Oncovirologie et Biothérapies, Centre Léon Bérard, 69008 Lyon, France

2 Hôpital Edouard Herriot, Service d'Hématologie, Pavillon E, Lyon, France

3 CHU d'Angers, Laboratoire d'Hématologie, Angers, France

4 CHU Henri Mondor, Laboratoire d'Immunologie, Créteil, France

5 Institut Pasteur, Unité d'Epidémiologie et Physiopathologie desVirus Oncogènes, Institut Pasteur, Paris, France

6 Fondation Rothschild, Service de Neurologie, Paris, France

7 Current address: Hémato-oncologie, Hôpital Saint-Louis, APHP, Université Paris VII, 1 avenue Claude Vellefaux, 75010 Paris, France

For all author emails, please log on.

Retrovirology 2010, 7:17  doi:10.1186/1742-4690-7-17

Published: 11 March 2010



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.


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.


Therefore, virus-cell interactions alone are not sufficient to initiate early leukemogenesis in vivo.