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  • Title: Studies of the immortalizing activity of HTLV type 1 Tax, using an infectious molecular clone and transgenic mice.
    Author: Ratner L, Portis T, Robek M, Harding J, Grossman W.
    Journal: AIDS Res Hum Retroviruses; 2000 Nov 01; 16(16):1647-51. PubMed ID: 11080805.
    Abstract:
    Expression of Tax in the mature lymphoid compartment of transgenic mice resulted in a lymphoproliferative malignancy of natural killer cells and cytotoxic T lymphocytes. Transgenic mouse tumors exhibited mutations in the p53 tumor suppressor gene, and functional inactivation of wild-type p53 protein. Tax transgenic mice heterozygous for the p53 gene exhibited more rapid tumor dissemination and accelerated mortality. Studies of Tax trans-activation in an infectious clone of HTLV-1 demonstrated a critical role for nuclear factor B activation in lymphocyte immortalization. A mutant disrupting Tax activation of the cAMP response element binding (CREB) protein resulted in preferential immortalization of CD8(+) lymphocytes, rather than preferential immortalization of CD4(+) lymphocytes seen with the wild-type infectious clone. A mutation disrupting Tax interaction with CREB-binding protein, CBP, did not affect lymphocyte immortalization by the infectious molecular clone. These models provide new insights into the molecular details of HTLV-1 leukemogenesis.
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