CANVENTOL INHIBITS HIV-1 REPLICATION BY A TAT-INDUCED TAR-INDEPENDENTMECHANISM

Canventol (2-isopropyl-4-isopropyldencyclohex-2-ene-1-ol), a blocker o f tumor necrosis factor alpha (TNF-alpha) release, inhibits human immu nodeficiency virus type (HIV-1) production in chronically and acutely infected cells. This effect of Canventol on virus replication could be correlated with its inhibitory influence on necrosis factor (NF)-kapp a B activation and HIV-1 long terminal repeat (LTR)-driven reporter ge ne expression in Jurkat cells and these could be overcome by the admin istration of TNF-alpha. Canventol inhibits activation of the promoter by the viral protein Tat through a TAR-independent mechanism. The HIV- 1 promoter is synergistically upregulated when both the TAR-independen t and the TAR-dependent modes of Tat action are in operation, Tat-indu ced downstream events, such as the production of cytokines like TNF-al pha and NF-kappa B activation, are central for this upregulation. Inhi bitors of the respective modes of action of Tat downregulate HIV-1 LTR activation and virus replication.