Structural and functional evidence that initiation and elongation of HIV-1 reverse transcription are distinct processes

Abstract

Retroviral reverse transcription starts with the extension of a cellular tRNA primer bound near the 5′ end of the viral genomic RNA at a site called the primer binding site (PBS). Formation of the HIV-1 initiation complex between tRNA 3 Lys, viral RNA and reverse transcriptase probably occurs during encapsidation of these components. tRNA 3 Lys is thought to be selectively packaged by interaction with the reverse transcriptase domain of the Pr160 Gag-Pol precursor protein, then annealed to the PBS of viral RNA with the help of the nucleocapsid protein. tRNA 3 Lys and HIV-1 viral RNA form a highly-structured complex, with extended interactions between the two molecules. Two different modes of reverse transcription have been distinguished: initiation, a tRNA 3 Lys-specific and distributive mode of polymerization corresponding to the addition of the first five nucleotides, followed by elongation, a non-specific and processive mode of DNA synthesis. These two modes are reminiscent of the initiation and elongation processes previously observed with DNA-dependent RNA polymerases.