In the first part of reverse transcription, minus-strand synthesis, a DNA strand complementary to the HIV genomic RNA is synthesized, using the viral RNA as a template and a host cell lysine tRNA molecule as primer. The synthesis proceeds in two discrete steps, separated by a strand transfer event. As minus strand DNA is synthesized, the viral genomic RNA is degraded, also in several discrete steps. Two specific polypurine tracts (PPT sequences) in the viral RNA, one within the pol gene (central or cPPT) and one immediately preceding the U3 sequence (3' PPT) are spared from degradation and serve to prime synthesis of DNA complementary to the minus strand (plus-strand synthesis). During plus-strand synthesis, Preston and colleagues observed secondary sites of plus-strand initiation at low frequency both in the cell-free system and in cultured virus (Klarman et al., 1997). Both DNA synthesis and RNA degradation activities are catalyzed by the HIV-1 reverse transcriptase (RT) heterodimer.