Human immunodeficiency virus type 1 (HIV-1) can infect quiescent cells, however, viral production is restricted to actively proliferating cells. Recent evidence has indicated that HIV-1 viral proteins, Vpr and Tat, perturb the cell cycle to optimize HIV-1 replication. Vpr arrests the cell cycle at G2 by inactivating the cyclin B / cdk1 complex. Tat regulates the cell cycle by altering factors involved in proliferation and differentiation (i.e. the cdk inhibitor p21 / waf1) and associating with cyclin / cdk complexes (i.e. cyclin E / cdk2, cyclin H / cdk7, and cyclin T / cdk9). These studies indicate the importance of host cellular factors, such as cyclin / cdk complexes, in regulating HIV-1 replication and therefore represent novel targets for antiviral therapeutics. Recently, the efficacy of pharmalogical cdk inhibitors (PCIs) in abrogating viral replication has been under development. To date there are 25-30 PCIs that have been synthesized against known cdks, several of which have been shown to inhibit HIV-1 and other AIDS-associated viruses in vitro and in vivo. Targeting these critical cyclin / cdk complexes needed for viral propagation may solve the problems inherent in current HAART therapy, including the emergence of drug-resistant viruses. Thus, PCIs have the potential to become novel therapeutic antiviral drugs that can inhibit HIV-1 transcription and opens the possibility of new avenues of treatment.
Keywords: HIV-1,, Tat,, latency,, cell cycle,, transcription,, pharmalogical cyclin-dependent kinase inhibitors (PCIs),, antiviral drugs
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