Reverse Transcriptase And Aids
Soon after AIDS was recognized in the early 1980s, Luc Montagneer of France and, subsequently, the American Robert Gallo determined that the causative agent was a retrovirus. Like other retroviruses, HIV-1 contains reverse transcriptase and must generate DNA. Differences between reverse transcriptase and cellular DNA polymerases in the sorts of DNA precursors (nucleosides) that they can utilize have been exploited to develop drugs that are selectively toxic to HIV-1.
Azidothymidine (AZT) is an example of a nucleoside analog DNA precursor that can serve as a reverse transcriptase "suicide inhibitor," because AZT incorporation into viral DNA prevents later steps in viral replication. However, the effectiveness of these sorts of drugs is limited by several factors. AZT is occasionally incorporated into cellular DNA, which contributes to the toxicity some patients experience when treated with reverse transcriptase inhibitors. Additionally, reverse transcriptase inhibitor resistance often develops during antiretroviral therapy. This resistance results from reverse transcriptase's high error rate, which generates a remarkable amount of genetic variation within HIV populations. If some viral genetic variants are less sensitive to antivirals than other variants, the resistant mutants will replicate during antiviral therapy. Despite these complications, reverse transcriptase inhibitors remain important components of the combined antiviral regimen that has dramatically lengthened the lives of many HIV-infected patients since the mid-1990s.
- Reverse Transcriptase - Reverse Transcription And The Human Genome
- Reverse Transcriptase - Laboratory Uses Of Reverse Transcriptase
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