Human immunodeficiency virus gene regulation as a target for antiviral chemotherapy.

摘要

Inhibitors interfering with human immunodeficiency virus (HIV) gene regulation may have great potential in anti-HIV drug (combination) therapy. They act against different targets to currently used anti-HIV drugs, reduce virus production from acute and chronically infected cells and are anticipated to elicit less virus drug resistance. Several agents have already proven to inhibit HIV gene regulation in vitro. A first class of compounds interacts with cellular factors that bind to the long terminal repeat (LTR) promoter and that are needed for basal level transcription, such as NF-kappa B and Sp1 inhibitors. A second class of compounds specifically inhibits the transactivation of the HIV LTR promoter by the viral Tat protein, such as the peptoid CGP64222. A third class of compounds prevents the accumulation of single and unspliced mRNAs through inhibition of the viral regulator protein Rev, such as the aminoglycosidic antibiotics. Most of these compounds have been tested in specific transactivation assays. Whether they are active at the postulated target in virus replication assays has, for many of them, not been ascertained. Toxicity data are often lacking or insufficient. Yet these data are crucial in view of the toxicity that may be expected for compounds that primarily interact with cellular factors. Although a promising lead, considerable research is still required before gene regulation inhibitors may come of age as clinically useful agents.