Figure 2

Schematic representation of reverse transcription in lentiviruses and other orthoretroviruses (such as MLV). The conversion of the single-strand RNA genome (represented as a black line) into double stranded DNA genome (at the bottom of the diagram) is the hallmark of retroviruses. Reverse transcription is initiated by the synthesis of minus-strand DNA (in green) at the PBS site (Primer Binding Site) at the 5' end of the RNA genome. The minus-strand strong-stop DNA thus synthesised is then transferred to the 3' end of the genome through complementarity with the R (Repeated) region of the LTR region (Long-Terminal Region) thus allowing synthesis of the minus-strand DNA to be completed. Minus strand DNA synthesis is accompanied by progressive degradation of the RNA matrix by the RNase H activity of reverse transcriptase. Two RNA sequences resist RNase degradation because they contain a unique PPT sequence and these serve as initiation sites for the plus-strand DNA. In all retroviruses, plus-strand DNA synthesis (in red) is initiated at the 3'PPT. In the case of lentiviruses, initiation also takes place at the cPPT. After a second strand transfer, plus-strand DNA synthesis proceeds to generate double-stranded DNA. In the case of lentiviruses, plus-strand initiation in two distinct sites leads to a displacement of the downstream strand over ca 100 nucleotides, terminating at the CTS and thus generating a discrete strand displacement called the central DNA Flap.