Mechanisms of Tax Regulation of Human T Cell Leukemia Virus Type I Gene Expression.

During the last several years, the human T cell leukemia virus type I (HTLV-I) has become recognized as an important cause for public health concern throughout the world. HTLV-I is the causative agent of a variety of clinical diseases, including an aggressive lymphoproliferative disorder named adult T cell leukemia. HTLV-I induces pathogenicity in the infected host cell through the synthesis of a virally encoded protein called Tax. Expression of Tax is critical to the life cycle of the virus, as the protein greatly increases the efficiency of HTLV-I gene transcription and replication. Furthermore, Tax has been shown to deregulate the transcription of many cellular genes, leading to the hypothesis that the presence of Tax promotes unchecked growth in the HTLV-I-infected cell. The mechanism of Tax trans-activation of HTLV-I gene expression is not known. Tax does not bind directly to the Tax-responsive promoter elements of the virus, but appears to function through interaction with certain cellular DNA binding proteins, including activating transcription factor 2 and cAMP response element binding protein that recognize these sequences. This review summarizes some of the recent work in the field aimed at elucidating the mechanism of Tax trans-activation of HTLV-I gene expression. Copyright 1995 S. Karger AG, Basel