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, exactly how viruses are down-regulated in vivo remains unresolved. We described here the possibility that down-regulation results from the presence of inhibitory elements within the gag-env region of the provirus in fresh peripheral blood mononuclear cells from carriers. In vitro experiments then revealed that potent cis-acting inhibitory elements (CIEs) 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 the HTLV-1 posttranscriptional regulator Rex through binding to the Rex-responsive element (RxRE), suggesting that Rex might interfere with pre-mRNA degradation and/or activate the export of mRNA molecules harboring both of the inhibitory elements and RxRE on the same RNA molecule. Thus, we propose the hypothesis that such functions of CIEs may be involved in HTLV-1 persistence.