Recombinant HIV-1 nucleocapsid protein accelerates HIV-1 reverse transcriptase catalyzed DNA strand transfer reactions and modulates RNase H activity

Abstract

The effect of recombinant nucleocapsid protein (NCp7) from human immunodeficiency virus type 1 (HIV-1) on HIV-1 reverse transcriptase (HIV-1 RT) catalyzed DNA strand transfer reactions has been studied using kinetic methods with a defined template--primer model system. NCp7 is shown to modulate both the rate and the efficiency of DNA strand transfer synthesis. Evidence is presented that supports the role of NCp7 in catalyzing the annealing of a nascent DNA intermediate and RNA acceptor template during strand transfer. NCp7 was also found to enhance the ribonuclease H activity of HIV-1 RT and change the specificity of RNA hydrolysis, suggesting a direct role of NCp7 in HIV-1 RT catalyzed strand transfer. The implications of these findings for retroviral reverse transcription are addressed.