The Selective Packaging and Annealing of Primer tRNALys3 in HIV-1

In HIV-1, tRNALys3 serves as the primer for reverse transcriptase, and during viral assembly, the tRNALys isoacceptors, tRNALys1,2 and tRNALys3, are selectively packaged into the virion. In this review, we shall first discuss the evidence for the formation of a tRNALys packaging complex, whose components include Gag, GagPol, genomic RNA, lysyl-tRNA synthetase (LysRS), and tRNALys. Evidence suggests that the formation of this complex involves a Gag / GagPol / viral genomic RNA complex interacting with a tRNALys / LysRS complex, with Gag interacting with both GagPol and LysRS, and GagPol interacting with the tRNALys. The interaction of Gag with LysRS is quite specific, does not require the presence of tRNALys, and LysRS is believed to be the target that allows the specific packaging of tRNALys into the virion. The parameters influencing these interactions, and the molecular sites of interaction, will be discussed. The selective packaging of tRNALys3 into HIV-1 facilitates annealing of tRNALys3 to the 5' region of viral RNA genome. This region contains a series of stem loops, and there exists several regions in both the viral RNA and the tRNALys3 that are believed to be important for tRNALys3 annealing. The annealing is facilitated by viral proteins such as unprocessed Gag, nucleocapsid, and reverse transcriptase.