Initiation of HIV-1 reverse transcription and functional role of nucleocapsid-mediated tRNA/viral genome interactions

HIV-1 reverse transcription is initiated from a tRNALys3 molecule annealed to the viral RNA at the primer binding site (PBS). The annealing of tRNALys3 requires the opening of its three-dimensional structure and RNA rearrangements to form an efficient initiation complex recognized by the reverse transcriptase. This annealing is mediated by the nucleocapsid protein (NC). In this paper, we first review the actual knowledge about HIV-1 viral RNA and tRNALys3 structures. Then, we summarize the studies explaining how NC chaperones the formation of the tRNALys3/PBS binary complex. Additional NMR data that investigated the NC interaction with tRNALys3 D-loop are presented. Lastly, we focused on the additional interactions occurring between tRNALys3 and the viral RNA and showed that they are dependent on HIV-1 isolates, i.e. the sequence and the structure of the viral RNA.

► A model for the NC-mediated formation of the tRNALys3/PBS complex is proposed.
► The structure of the tRNALys3/vRNA complex is depent on the vRNA structure.
► Additional interactions between tRNALys3 and viral RNA are discussed.