Figure 4. Substrates for Gag-facilitated RNA refolding events that occur during HIV-1 assembly.

HIV-1 Gag catalyzes annealing of the primer tRNA^Lys3 (ii) to complementary regions on the viral genome (i). Three regions of tRNA^Lys3 (1, 2, 3, red) interact with 3 complementary regions on the genome (1*, 2*, 3*, red). The highly conserved 18-nt PBS (1*) is complementary to the 3′ 18 nt (1) of tRNA^Lys3. Reverse transcription initiates from the 3′-hydroxyl of A76. Regions 2* and 3* have been proposed to interact with the anticodon stem and variable arm (2) and anticodon loop (3), respectively, but their roles in tRNA^Lys3 priming are not as well established. The 2/2* interaction is important for efficient initiation of cDNA synthesis [83], and a similar interaction occurs in RSV [84]. The 3/3* interaction between the U-rich tRNA^Lys3 anticodon and A-rich bulge upstream of the PBS has been proposed to help stabilize the tRNA^Lys3 primer [85]. These interactions are consistent with SHAPE analysis of the genome [53].