Approximately 20 million people are infected with Human T-cell Leukemia Virus type 1 (HTLV-1), and about 6% of this population will develop a pathology associated with this retrovirus. One of these diseases is called adult T-cell leukemia/lymphoma (ATLL). ATLL is an aggressive and often fatal proliferation of T CD4+ lymphocytes that can occur after a viral latency period of more than twenty years. To date, there is no effective treatment for ATLL, and individuals diagnosed with the most severe stage of the disease have a mean survival time of six months. The molecular mechanisms leading to the development of ATLL are unclear, although the virally-encoded protein Tax is postulated to have a role in disease progression. The low percentage of infected individuals who develop ATLL and the long latency period suggest that multiple events are required for T-cell transformation. Therefore, defining the mechanisms through which HTLV-1 infection leads to ATLL will increase our understanding of the cellular transformation process in general.

Our research focuses on characterizing the roles of the virally-encoded proteins Tax and HBZ in HTLV-1 transcriptional regulation and in the disruption of cellular gene expression. Tax functions as a transcription factor and, in conjunction with a number of cellular factors that include members of the ATF/CREB family, strongly activates transcription of the HTLV-1 genome. Tax also has oncogenic properties that stem from its ability to deregulate transcription of a number of cellular genes. Less is known about the HBZ protein, which was identified only recently. To date, HBZ has been shown to repress transcription through its interaction with a subset of cellular bZIP proteins, including certain ATF/CREB members. Of specific interest to us is the ability of HBZ to repress transcription driven by the HTLV-1 promoter. In order to define the functions of Tax and HBZ in viral infection, we are analyzing protein/DNA interactions within the cell and in vitro, and determining how these viral proteins affect transcription.

Landry S., Halin M., Vargas A., Lemasson I., Mesnard J.M. and Barbeau B. (2009).  Upregulation of HTLV-1 antisense transcription by the viral Tax protein.  J. Virol., 83 (4):2048-54.

Clerc I., Polakowski N., André-Arpin C., Cook P., Barbeau B., Mesnard J.M. and Lemasson I.  (2008).  An interaction between the human T cell leukemia virus type 1 basic leucine zipper factor (HBZ) and the KIX domain of p300/CBP contributes to the down-regulation of tax-dependent viral transcription by HBZ. J. Biol. Chem., 283 (35):23903-23913.

Lemasson I., Lewis M., Polakowski N., Hivin P., Cavanagh M.H., Thébault S., Barbeau B., Nyborg J.K. and Mesnard J.M.  (2007).  HTLV-1 bZIP protein interacts with the cellular transcription factor CREB to inhibit HTLV-1 transcription.  J. Virol., 81 (4):1543-1553.

Lemasson I., Polakowski N., Laybourn P.J. and Nyborg J.K. (2006). Tax-dependent displacement of nucleosomes during transcriptional activation of human T-cell leukemia virus, type 1. J. Biol. Chem.,  281 (19): 13075-13082.

Lemasson I., Polakowski N., Laybourn P.J. and Nyborg J.K. (2004). Transcription regulatory complexes bind the human T-cell leukemia virus 5’ and 3’ long terminal repeats to control gene expression. Mol. Cell. Biol., 24 (14): 6117-6126.

Lemasson I., Polakowski N., Laybourn P.J. and Nyborg J.K.(2002). Transcription factor binding and histone modifications on the integrated proviral promoter in HTLV-I-infected T-cells. J. Biol. Chem., 277 (51): 49459-49465.

Lemasson I. and Nyborg J.K. (2001). HTLV-I Tax repression of p73b is mediated through competition for the C/H1 domain of CBP. J. Biol. Chem., 276 (19): 15720-15727.

Giebler H., Lemasson I. and Nyborg J.K. (2000). P53 recruitment of CBP mediated through phosphorylated CREB: a novel pathway for tumor suppressor regulation. Mol. Cell. Biol., 20 (13): 4849-4858.

Lemasson I., Thébault S., Sardet C., Devaux C. and Mesnard J.M. (1998). Activation of E2F-mediated transcription by human T-cell leukemia virus type I Tax protein in a p16INK4A negative T-cell line. J. Biol. Chem., 273 (36): 23598-23604.

Lemasson I., Robert-Hebmann V., Hamaia S., Duc Dodon M., Gazzolo L. and Devaux C. (1997). Transrepression of lck gene expression by human T-cell leukemia virus type I-encoded p40tax. J. Virol., 71: 1975-1983.

NIH PubMed Publications List for Isabelle Lemasson