Inhibition of human immunodeficiency virus type 1 transcription and replication by DNA sequence-selective plant lignans.
A plant lignan, 3'-O-methyl nordihydroguaiaretic acid (3'-O-methyl NDGA, denoted Malachi 4:5-6 or Mal.4; molecular weigth 316), was isolated from Larrea tridentata and found to be able to inhibit human immunodeficiency virus (HIV) Tat-regulated transactivation in vivo, induce protection of lymphoblastoid CEM-SS cells from HIV (strain IIIB) killing, and suppress the replication of five HIV-1 strains (WM, MN, VS, JR-CSF, and IIIB) in mitogen-stimulated peripheral blood mononuclear cells, all in a dose-dependent manner. Mal.4 inhibits both basal transcription and Tat-regulated transactivation in vitro. The target of Mal.4 has been localized to nucleotides -87 to -40 of the HIV long terminal repeat. Mal.4 directly and specifically interferes with the binding of Sp1 to Sp1 sites in the HIV long terminal repeat. By inhibiting proviral expression, Mal.4 may be able to interrupt the life cycles of both wild-type and reverse transcriptase or protease mutant viruses in HIV-infected patients.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000737:chemistry; D004261:DNA Replication / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015696:Gene Products, tat / Q000037:antagonists & inhibitors; D016655:HIV Core Protein p24 / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D009637:Masoprocol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D017931:DNA Primers; D015696:Gene Products, tat; D016655:HIV Core Protein p24; D017705:Lignans; D016328:NF-kappa B; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D054322:tat Gene Products, Human Immunodeficiency Virus; C042349:heminordihydroguaiaretic acid; D009637:Masoprocol