Canventol inhibits HIV-1 replication by Tat-induced Tar-independent mechanism.
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.
Biswas
D K
DK
Division of Cell Growth and Regulation, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, U.S.A.
Tius
M A
MA
Zhuo
J
J
Pardee
A B
AB
D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001483:Base Sequence; D001569:Benzodiazepines / Q000008:administration & dosage; D002460:Cell Line; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D015696:Gene Products, tat / Q000235:genetics / Q000502:physiology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011758:Pyrroles; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D003511:Cyclohexanols; D015696:Gene Products, tat; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; D001569:Benzodiazepines; C070024:Ro 24-7429; C082453:canventol