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Science 20 December 1991:
Vol. 254. no. 5039, pp. 1799 - 1802
DOI: 10.1126/science.1763331
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Articles

Science, Vol 254, Issue 5039, 1799-1802
Copyright © 1991 by American Association for the Advancement of Science

articles

Inhibition of HIV replication in acute and chronic infections in vitro by a Tat antagonist

MC Hsu, AD Schutt, M Holly, LW Slice, MI Sherman, DD Richman, MJ Potash, and DJ Volsky

Department of Virology, Hoffmann-La Roche, Nutley, NJ 07110.

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.


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