The HIV-1 reverse transcription (RT) process as target for RT inhibitors.
Since the Human Immunodeficiency Virus Type 1 (HIV-1) was identified as the etiologic agent of the Acquired Immune Deficiency Syndrome (AIDS), the HIV-1 reverse transcriptase (RT) has been the subject of intensive study. The reverse transcription entails the transition of the single-stranded viral RNA into double-stranded proviral DNA, which is then integrated into the host chromosome. Therefore, the HIV-1 reverse transcriptase plays a pivotal role in the life cycle of the virus and is consequently an interesting target for anti-HIV drug therapy. In the first section, we describe the complex process of reverse transcription and the different activities involved in this process. We then highlight the structure-function relationship of the HIV-1 reverse transcriptase, which is of great importance for a better understanding of resistance development, a major problem in anti-AIDS therapies. Finally, we summarize the mechanisms of HIV resistance toward various RT inhibitors and the implications thereof for the current anti-HIV drug therapies.
Jonckheere
H
H
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Anné
J
J
De Clercq
E
E
D019380:Anti-HIV Agents / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D011487:Protein Conformation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase