Document 0342
 DOCN  M94A0342
 TI    Organic thiophosphate WR-151327 suppresses expression of HIV in
       chronically infected cells.
 DT    9412
 AU    Kalebic T; Schein PS; Laboratory of Molecular Genetics, National Cancer
       Institute,; National Institutes of Health, Bethesda, Maryland 20892.
 SO    AIDS Res Hum Retroviruses. 1994 Jun;10(6):727-33. Unique Identifier :
       AIDSLINE MED/94355119
 AB    Reducing agents such as glutathione (GSH), glutathione ester (GSE), and
       N-acetylcysteine (NAC) have been shown to suppress the induction of HIV
       expression in chronically infected cells stimulated by cytokines. We
       present data which show the effects of the organic thiophosphate
       WR-151327 on the expression of latent HIV in U1 cells. The chronically
       infected promonocytic cell line U1 constitutively expresses low levels
       of HIV that can be increased by 13-phorbol 12-myristate acetate (PMA),
       tumor necrosis factor alpha (TNF-alpha), and granulocyte/monocyte
       colony-stimulating factor (GM-CSF). WR-151327 suppressed, in
       dose-dependent fashion, the reverse transcriptase (RT) activity induced
       by TNF-alpha, GM-CSF, and PMA. The maximal decrease in RT activity was
       70, 80, and 50%, respectively. Pretreatment with WR-151327 also
       suppressed the induction of total HIV protein synthesis, as shown by
       Western blot analysis. In addition, WR-151327 suppressed HIV-LTR-CAT
       activity in transfected human rhabdomyosarcoma cells (RD). Suppression
       of HIV expression by WR-151327 was observed in the absence of a
       cytotoxic or cytostatic effect. Incubation of WR-151327 with human
       recombinant TNF-alpha for 6 hr at 37 degrees C did not alter the
       capacity of TNF-alpha to induce the expression of HIV. Our observations
       further support the hypothesis that reducing agents are important in the
       control of HIV replication and that the clinical evaluation of WR-151327
       may be indicated.
 DE    Amifostine/ANALOGS & DERIVATIVES/*PHARMACOLOGY  Cell Line/DRUG
       EFFECTS/MICROBIOLOGY  Cytokines/PHARMACOLOGY  HIV Infections/*DRUG
       THERAPY  HIV-1/*DRUG EFFECTS  Organothiophosphorus
       Compounds/*PHARMACOLOGY  Reverse Transcriptase/METABOLISM  Sulfhydryl
       Compounds/PHARMACOLOGY  JOURNAL ARTICLE

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