Differential effects of intronic and exonic locations of the human immunodeficiency virus type 1 Rev-responsive element.

The influence of the location of the Rev-response element (RRE) on human immunodeficiency virus type 1 (HIV-1) protein and RNA expression in COS cells was assessed. The RRE was placed into nef where it would be present in all HIV-1 RNAs. At this location, Gag and Env proteins were produced and the unspliced gag/pol and partially spliced env/vpu RNAs were able to accumulate in the cytoplasm. The RRE was also relocated from its normal location in the env exon to the env intron. In this way, the RRE would be present in the nuclear env pre-mRNA, but not in the spliced env mRNA. Gag, but not Env protein production was detected. Th presence of the RRE in the env pre-mRNA allowed the cytoplasmic accumulation of the spliced env mRNA, which lacked the RRE. However, this mRNA accumulated at a reduced level relative to that produced by constructs containing the RRE within the env mRNA. The cytoplasmic accumulation of this mRNA was dependent on the presence of Rev and the RRE. These results demonstrate that the location of the RRE can have differential effects on the fate of HIV-1 RNAs.