Regulation of HTLV-II gene expression by rex involves positive and negative cis-acting elements in the 5′ long terminal repeat

Regulation of human T-cell leukemia virus type II (HTLV-II) gene expression by the trans-acting viral protein, Rex, is mediated through specific cis-acting sequences in the HTLV-II long terminal repeat (LTR). Augmentation of 5′ LTR-linked gene expression by Rex requires two distinct cis-acting elements: one termed the "Rex-responsive element" (RxRE), which allows Rex to overcome the inhibitory effect of a second, termed the "cis-acting repressive sequences" (CRS). The HTLV-II RxRE is located between nt +91 and +317 relative to the cap site in the R/U5 region of the 5′ LTR, and the HTLV-II CRS is contained within the RxRE from nt +208 to +317, which is downstream of the splice donor site, in the R/U5 region of the 5′ LTR. Deletion of the CRS results in significantly increased cytoplasmic levels of LTR-linked mRNA independent of the presence of Rex. Our results show that Rex acts post-transcriptionally and induces a shift from nucleus to cytoplasm of gag/pol mRNA, the only HTLV-II mRNA that contains both the RxRE and the CRS in the 5′ LTR-derived leader sequence.