Our aim was to investigate whether the presence of TAR affects HIV-1 frameshift efficiency in relationship with its effect on cap-dependent translation initiation. To this end, we used a dual-luciferase construct, pDual-HIV(-1), which contains the Rluc and the Fluc reporter genes separated by the HIV-1 frameshift region ( Figure 1B ). In this construct, the Fluc is produced only by ribosomes that make a -1 frameshift when translating the HIV-1 frameshift region. To assess the frameshift efficiency, we used a control construct, pDual-HIV(0), in which an adenine is added after the slippery sequence in the frameshift region, so that the Fluc coding sequence is in-frame with the Rluc coding sequence. The Rluc is synthesized by conventional translation in both (-1) and (0) constructs. Before investigating the effect of TAR, we verified that changes in cap-dependent translation initiation affect HIV-1 frameshift efficiency. Jurkat cells, a CD4+ T-cell line, were transfected with pDual-HIV(-1) or (0) plasmids and treated with thapsigargin, rapamycin or hippuristanol, three inhibitors perturbing a different step of capdependent translation initiation ( Figure 1A ). The frameshift efficiency, which is 5.1 AE 0.4% in the absence of inhibitors, was increased about twofold in the presence of either one of these three inhibitors ( Figure 1C) .