Inhibition of HIV Replication in Acute and Chronic Infections in Vitro by a Tat Antagonist
| Autor: | Ming-Chu Hsu, Douglas D. Richman, Mary Jane Potash, Lee W. Slice, David J. Volsky, Andrew D. Schutt, Maureen Holly, Michael I. Sherman |
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| Rok vydání: | 1991 |
| Předmět: |
viruses
Biology Virus Replication Antiviral Agents Virus Cell Line law.invention Antigen law Gene expression Humans Pyrroles Promoter Regions Genetic HIV Long Terminal Repeat Benzodiazepinones Multidisciplinary Transfection Virology In vitro Kinetics Viral replication Cell culture Gene Products tat HIV-2 HIV-1 Recombinant DNA tat Gene Products Human Immunodeficiency Virus Zidovudine |
| Zdroj: | Science. 254:1799-1802 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.1763331 |
| Popis: | The human immunodeficiency virus-1 (HIV-1) trans-activator Tat is an attractive target for the development of antiviral drugs because inhibition of Tat would arrest the virus at an early stage. The drug Ro 5-3335 [7-chloro-5-(2-pyrryl)-3H-1,4-benzodiazepine-2(H)-one], inhibited gene expression by HIV-1 at the level of transcriptional trans-activation by Tat. The compound did not inhibit the basal activity of the promoter. Both Tat and its target sequence TAR were required for the observed inhibitory activity. Ro 5-3335 reduced the amount of cell-associated viral RNA and antigen in acutely, as well as in chronically infected cells in vitro (median inhibition concentration 0.1 to 1 micromolar). Effective inhibition of viral replication was also observed 24 hours after cells were transfected with infectious recombinant HIV-1 DNA. The compound was active against both HIV-1 and HIV-2 and against 3'-azido-3'-deoxythymidine (AZT)-resistant clinical isolates. |
| Databáze: | OpenAIRE |
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