Effects of GLQ223 on HIV replication in human monocyte/macrophages chronically infected in vitro with HIV.

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

Effects of GLQ223 on HIV replication in human monocyte/macrophages chronically infected in vitro with HIV.

AIDS Res Hum Retroviruses. 1990 Aug;6(8):1039-43. Unique Identifier : AIDSLINE MED/91026269
McGrath MS; Santulli S; Gaston I; Department of Medicine, University of California, San Francisco.

Abstract: GLQ223 is a formulated version of tricosanthin, a single-chain ribosome-inactivating protein that was shown in earlier studies to inhibit human immunodeficiency virus (HIV) replication in T-lymphoblastoid cells and to decrease HIV p24 levels in HIV-infected monocyte-derived macrophages as measured by flow cytometry. The current studies were performed to test the selectivity of the observed inhibitory effects on HIV replication in chronically infected macrophages infected in vitro. Peripheral blood-derived monocyte/macrophages were infected in vitro and cultivated in suspension for at least two weeks prior to GLQ223 treatment. Anti-HIV effects were quantitated by measurement of cytoplasmic HIV p24, by both enzyme-linked immunosorbent assay (ELISA) and flow cytometry and HIV RNA levels were measured by slot blot analysis. Incorporation of [3H]leucine into trichloroacetic acid- (TCA) precipitable protein was also evaluated as an index of nonspecific inhibitory effects mediated by the compound in infected and uninfected cultures. Five days after a single 3-h treatment with GLQ223 there was a concentration-dependent decrease in all measurable HIV parameters within infected cultures. The anti-HIV effects persisted at least 28 days without evidence for increasing HIV expression. GLQ223 treatment of parallel uninfected macrophage cultures showed no significant inhibition of tritiated leucine uptake. These experiments demonstrate that a single pulsed exposure with GLQ223 of macrophages infected with HIV in vitro caused a sustained, concentration-dependent decrease in both HIV p24 antigen levels as well as HIV RNA without causing measurable toxicity in uninfected cultures.

Keywords: Antiviral Agents/ADMINISTRATION & DOSAGE/*PHARMACOLOGY Dose-Response Relationship, Drug Human HIV/*DRUG EFFECTS/GROWTH & DEVELOPMENT HIV Infections/*DRUG THERAPY In Vitro Macrophages/DRUG EFFECTS/*MICROBIOLOGY Monocytes/DRUG EFFECTS/*MICROBIOLOGY Trichosanthin/ADMINISTRATION & DOSAGE/*PHARMACOLOGY Virus Replication/DRUG EFFECTS JOURNAL ARTICLE
910228
M9120685

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