Review Article

HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions

Figure 1

HIV-1 reverse transcription process. Step 1: host cell tRNALys3 hybridizes to the PBS near the 5′-end of the (+)strand RNA genome (orange). (−)strand DNA (blue) synthesis starts using host tRNALys3 as a primer. DNA synthesis proceeds up to the 5′-end of the RNA genome. Step 2: RNase H hydrolysis of the RNA portion of the RNA:DNA hybrid product exposes the ssDNA product determining the (−)strand strong stop DNA. Step 3: strand transfer of the (−)strand DNA through its hybridization with the R region at the 3′-end of the ssRNA genome and further elongation of the (−)strand DNA. Step 4: DNA synthesis proceeds, and the RNase H function cleaves the RNA strand of the RNA:DNA at numerous points leaving intact two specific sequences (cPPT, 3′PPT) resistant to the RNase H cleavage. Step 5: (−)strand DNA synthesis (green) initiation using PPTs as primers. Step 6: RNase H hydrolysis of the PPT segments and the junction of the tRNA:DNA hybrid, freeing the PBS sequence of the (+)strand DNA. Step 8: strand transfer of the PBS sequence of the (+)strand DNA that anneals to the PBS on the (−)strand DNA. DNA synthesis then continues with strand displacement synthesis. Step 9: the product is a linear dsDNA with long terminal repeats (LTRs) at both ends.
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