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 during minus strand DNA synthesis and prime plus-strand synthesis. At least two discrete steps of DNA replication, removal of the PPT RNAs and the tRNA primer that initiated minus-strand synthesis, and a strand transfer lead to the synthesis of a linear duplex DNA corresponding to the full length of the HIV genomic RNA with long terminal repeat (LTR) sequences at both ends. Both DNA synthesis and RNA degradation are catalyzed by domains of the HIV-1 reverse transcriptase (RT) heterodimer. 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-infected cells (Klarman et al., 1997).