The human T cell lymphotropic virus 1 (HTLV-1): cellular and molecular characterization of the HTLV-1 oncogenic protein HBZ.

T cell leukemia virus type 1 (HTLV-1 ) is the etiological agent responsible of a severe form of hematologic malignancy designated Adult T cell Leukemia/Lymphoma or ATLL and of aneurological syndrome designated HTLV Associated Myelopathy/Tropical SpasticParaparesis or HAM/TSP. Although the major documented viral oncogenic product ofHTLV-1 is the Tax-1 protein, it has been recently demonstrated that also HBZ (HTLV-1 bZIPfactor), a protein encoded by the minus strand of HTLV-1 genome, is involved in thepathogenesis of ATL. The full role played by HBZ in oncogenesis is still to be explored indetail mainly owing to the unavailability of tools to study this protein in naturally infectedcells and in ATLL cells and its interaction with other crucial cellular proteins involved in thehomeostasis of cell activation and proliferation. By the use of the first reported monoclonalantibody against HBZ generated in our laboratory we have carefully analyzed HBZ proteinexpression, sub-cellular localization as well as its interaction in vivo with endogenous cellfactors in various HBZ-expressing cells, including in particular HTLV-1-infected cells andATLL tumor cell lines. We also demonstrated the ability of this monoclonal antibody to detectHBZ in fresh PBMCs of HTLV-1 infected patients. The availability of this newly generated anti-HBZ mAb has allowed for the first time the quantization of HBZ at the single cell level in naturally infected cells and in neoplastic cells, a better definition of HBZ expression, localization and functional involvement in the biology of HTLV-1 infected cells. The findings described in this thesis may help to better understand the mechanisms through which viral oncogenes contribute to immortalization and neoplastic