ro-24-7429 and canventol

Canventol (2-isopropyl-4-isopropyldencyclohex-2-ene-l-ol), a blocker of tumor necrosis factor alpha (TNF-alpha) release, inhibits human immunodeficiency 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)-kappa B activation and HIV-1 long terminal repeat (LTR)-driven reporter gene expression in Jurkat cells and these could be overcome by the administration 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-independent and the TAR-dependent modes of Tat action are in operation. Tat-induced downstream events, such as the production of cytokines like TNF-alpha and NF-kappa B activation, are central for this upregulation. Inhibitors of the respective modes of action of Tat downregulate HIV-1 LTR activation and virus replication.

Topics: Antiviral Agents; Base Sequence; Benzodiazepines; Cell Line; Cyclohexanols; Down-Regulation; Drug Synergism; Gene Products, tat; HIV Long Terminal Repeat; HIV-1; Humans; Molecular Sequence Data; NF-kappa B; Oligodeoxyribonucleotides; Promoter Regions, Genetic; Pyrroles; tat Gene Products, Human Immunodeficiency Virus; Transcriptional Activation; Tumor Necrosis Factor-alpha; Virus Replication