Analysis of Molecular Mechanisms that contribute to the development of HTLV-1 associated Pathologies

MARZIALI, F, VALDANO, M, FACCIUTO, F, CAVAORTA, A Y GARDIOL, D.

Buenos Aires

Workshop; 3rd ICGEB Workshop on Human RNA Virus; 2012

 Human T-cell Leukemia Virus type 1 (HTLV-1) is a retrovirus extensively distributed around the world and is associated to the development of two important diseases: Adult T-cell leukemia (ATL) and HTLV-associated myelopathy/Tropical spastic paraparesis (HAM/TSP). In Argentina, more specifically in the province of Jujuy, a high endemic region was identified. Many efforts have been made to elucidate the pathological molecular mechanisms of the viral infection; however, they are yet poorly understood. Recently, it was reported that the viral protein Tax has an essential role. An important feature of Tax is the presence of a C-terminal domain that interacts with PDZ motifs present in proteins that regulate the cell polarity and signal transduction pathways. This C-terminal PDZ binding domain was also found in the high risk HPV E6 protein and its oncogenic activity was well established. We propose to improve the characterization of the oncogenic functions of Tax and its relationship with T-cell activation. We will try to identify new cellular targets of Tax, specially those involved in cell polarity and signal transduction pathways, like members of the polarity protein complex. Furthermore, we are interested in investigating whether the Tax-PDZ binding can cause T-cell activation and proliferation.