Modes of transformation by the human T-cell leukemia viruses

Two pathogenic human retroviruses have been isolated and shown to cause diseases characterized by malignant proliferation of T-cells. Human T-cell leukemia virus type I (HTLV-I) is the virus etiologic agent of adult T-cell leukemia, and human T-cell leukemia virus type II (HTLV-II) has been rarely associated with some forms of leukemia related to hairy-cell leukemia. Understanding the pathogenesis of these retroviruses requires elucidating the mechanism by which HTLV immortalizes cells. Two hypothetical modes of HTLV-induced transformation are discussed in this review. At the cell surface, HTLV particles via as yet unknown receptors have mitogenic effects on T-cell growth. Once HTLV productively infects the cell, it can initiate molecular changes as well. The HTLV genome encodes a viral regulatory protein, Tax, which not only activates HTLV gene expression, but may also induce inappropriate expression of cellular genes involved in cell proliferation. Models are proposed for how these events mediated by HTLV may contribute to T-cell transformation and ultimately, leukemia.