Investigating Human T Cell Lymphotropic Retrovirus (HTLV) Tax Function with Molecular and Immunophenotypic Techniques
Human T cell Lymphotropic Viruses 1 and 2 (HTLV-1 and HTLV-2) are the first described human retroviruses. HTLV-1 is the causative agent of an aggressive malignancy of CD4+ T lymphocytes named adult T-cell leukemia/lymphoma (ATLL) and of a chronic neurological disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-2 shares many similarities with HTLV-1, but displays lower or absent association to diseases. Among the proteins encoded by HTLVs, the viral transactivator Tax exerts an essential role in viral transcription as well as in cell transformation. Different experimental methods to study Tax activity on HTLV-LTR promoter and Tax subcellular distribution are described. Emphasis is given to the functional and physical interaction between Tax-1/Tax-2 and cellular cofactors which may have an impact on the infectivity process of the HTLVs and on the capacity of cell transformation.
Key wordsDual luciferase reporter assay Co-immunoprecipitation Immunoblot Immuno-fluorescence Confocal microscopy
This work was supported by the following grants to RSA: Fondazione Cariplo 2008–2230 “Cellular and molecular basis of human retroviral-dependent pathology”; A.I.R.C IG 8862 “New strategies of tumor vaccination and immunotherapy based on optimized triggering of anti-tumor CD4+ T cells”; MIUR-PRIN project 2008-WXF7KK “New strategies of immunointervention against tumors”; University of Insubria “FAR 2009” and “FAR 2010” to GT.
- 18.Clerc I, Polakowski N, André-Arpin C et al (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 283:23903–23913PubMedCentralCrossRefPubMedGoogle Scholar