The x Gene Is Essential for HTLV Replication

Abstract

The human T-cell leukemia viruses (HTLV) are associated with T-cell malignancies in man and will transform normal human T cells in vitro. The mechanism of malignant transformation by HTLV is unknown but appears to be distinct from that of other classes of retroviruses, which induce malignant transformation through viral or cellular oncogenes. Recently a new gene, termed x, was identified in HTLV. This gene has been hypothesized to be the transforming gene of HTLV because of its conservation within the HTLV class of retroviruses. By in vitro mutagenesis of the HTLV-II x gene, it is now demonstrated that the presence of a functional x gene product is necessary for efficient HTLV transcription. Therefore, these studies provide direct evidence for an important function of the x gene in HTLV replication. The functional analogies between the x gene and transcriptional regulatory genes of some DNA viruses suggest that these viruses share similar mechanisms for cellular transformation.

Calcium-mediated inhibition of phorbol ester and Tax trans-activation of the human T cell leukaemia virus type 1

“…Positive regulators of HTLV-1 LTR-directed gene expression have been defined and include 12-0-tetradecanoylphorbol-13-acetate (TPA) (Radonovich & Jeang, 1989) and Tax (Chen et al, 1985;Radonovich & Jeang, 1989;Sodroski et al, 1985;Varmus, 1988). The response of the LTR to TPA-mediated T cell activation is determined by a 60 bp sequence which overlaps one Tax-responsive element (Radonovich & Jeang, 1989).…”

Comparison of the trans-activation capabilities of the human T-cell leukemia virus type I and II chi proteins.

“…Members of this group of retroviruses have in common a fourth gene not present in other retroviruses (15,23,30,32,33). This gene has been called the X gene (also variously termed lor, X-lor, and tat).The HTLV-I p40 and HTLV-Il p37 proteins encoded by this region are essential for HTLV replication and act by enhancing the rate of transcription by the HTLV long terminal repeats (LTRs) (3,6,8,35). This property of the HTLV X proteins is similar to that of other transcriptional regulatory proteins of DNA viruses such as adenoviruses, papovaviruses, and herpesviruses (for a review, see reference 21).…”

“…The HTLV-I p40 and HTLV-Il p37 proteins encoded by this region are essential for HTLV replication and act by enhancing the rate of transcription by the HTLV long terminal repeats (LTRs) (3,6,8,35). This property of the HTLV X proteins is similar to that of other transcriptional regulatory proteins of DNA viruses such as adenoviruses, papovaviruses, and herpesviruses (for a review, see reference 21).…”

Modulation of tax and PKA‐mediated expression of HTLV‐I promoter via cAMP response element binding and modulator proteins CREB and CREM

“…Tax is the viral gene product responsible for the autoregulation of the HTLV-I promoter and has been shown not to bind directly to target DNA [10,11]. Instead, Tax is believed to indirectly interact with CREs of the HTLV-I 21-bp repeats by forming protein-protein complexes with transcription factors [12,13].…”