Leung D, Peterson P, Gekker G, Chao C, Bursten S, Bianco J, Singer J; International Conference on AIDS.
Int Conf AIDS. 1994 Aug 7-12; 10: 33 (abstract no. 423A).
Cell Therapeutics, Inc., Seattle, WA 98119.
OBJECTIVE: To test whether an inhibitor of phosphatidic acid (PA) generation, CT-2576, would suppress the expression and replication of HIV in cells. METHODS: A reporter gene expression system under the control of the HIV-LTR promotor in 293-EBNA cells was set up as a surrogate marker to screen compounds that inhibit HIV-LTR directed expression through blocking of PA. The selected compounds were then tested for their capability of inhibiting HIV expression in the chronically HIV infected promonocyte U1 cell line. RESULTS: CT-2576 inhibited the activation of HIV-LTR promotor by tat or TNF-a with an IC50 value of about 5 microM with minimal cytotoxicity on 293-EBNA cells. CT-2576 was also effective in inhibiting CMV and SV40 early promotor activity but had little effect on the housekeeping gene, phosphoglycerate kinase, promotor activity. CT-2576 suppressed the constitutive expression as well as the TNF-a or IL-6 mediated induction of HIV-1 p24 antigen in U1 cells with an IC50 value of around 1 microM. DISCUSSIONS AND CONCLUSIONS: CT-2576 inhibited the cytokine-induced and tat-directed expression of HIV with minimal cytotoxicity. CT-2576 inhibited HIV expression by interfering with the intracellular signaling phospholipid PA which appears critical to cell activation. CT-2576 and other compounds that can suppress PA generation should be of therapeutic interest for delaying or preventing the onset of AIDS and certain other viral diseases in HIV-infected patients.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- CT 2576
- Cell Line
- Cytokines
- Gene Expression
- Gene Expression Regulation, Viral
- Gene Products, tat
- Genes, Reporter
- Genes, tat
- HIV
- HIV Infections
- HIV Long Terminal Repeat
- HIV Seropositivity
- Humans
- Interleukin-6
- Lipids
- Monocytes
- Signal Transduction
- Xanthines
- antagonists & inhibitors
- genetics
Other ID:
UI: 102210833
From Meeting Abstracts