Polyvalent Rev decoys act as artificial Rev-responsive elements

Interactions between Rev and the Rev-responsive element (RRE) control the o rder, rate, and extent of gene expression in human immunodeficiency virus t ype 1, Rev decoys may therefore prove to be useful RNA therapeutics for the treatment of AIDS. To improve upon the current generation of Rev decoys th at bind single Rev molecules, it would be useful to generate polyvalent Rev decoys that could bind multiple Rev molecules. J, Kjems and P, A, Sharp (J . Virol, 67:4769-4776, 1993) originally constructed functional polyvalent R ev decoys, but the structural context of these polyvalent decoys remains un clear, and it has been argued that the individual decoys were either struct urally discrete (Kjems and Sharp, J, Virol, 67:4769-4776, 1993) or were par t of an extended helix (R, W, Zemmel et al,, Mel. Biol, 258:763-777, 1996), To resolve the differences between these models, we have designed and synt hesized concatemers of Rev-binding elements (RBEs) that fold to form multip le, discrete, high-affinity Rev-binding sites. We find that the concatenate d RBEs can facilitate the cytoplasmic transport of viral mRNAs and therefor e likely bind multiple Rev molecules, These artificial RREs may simultaneou sly sequester Rev and hinder access to the cellular transport machinery.