CIS-ACTING INHIBITORY ELEMENTS WITHIN THE POL-ENV REGION OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 POSSIBLY INVOLVED IN VIRAL PERSISTENCE

Human T-cell leukemia virus type 1 (HTLV-1) remains latent throughout the life of the carrier, with cells containing the provirus and viral gene expression efficiently down-regulated. On a molecular level, exac tly how viruses are down-regulated in vivo remains unresolved. We desc ribed here the possibility that down-regulation results from the prese nce of inhibitory elements within the gag-env region of the provirus i n fresh peripheral blood mononuclear cells from carriers. In vitro exp eriments then revealed that potent cia-acting inhibitory elements (CIE s) are indeed contained in two discrete fragments from the pol region and weaker ones in the env region. The effect of CIEs is relieved by t he HTLV-1 posttranscriptional regulator Rex through binding to the Rex -responsive element (RxRE), suggesting that Rex might interfere with p re-mRNA degradation and/or activate the export of mRNA molecules harbo ring both of the inhibitory elements and RxRE on the same RNA molecule . Thus, we propose the hypothesis that such functions of CIEs may be i nvolved in HTLV-1 persistence.