title: Activation of the human immunodeficiency virus long terminal repeat in THP-1 cells by a staphylococcal extracellular product.
abstract: Staphylococcal strains can release a factor that strongly activates the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in THP-1 cells transfected with the HIV-1 LTR-driven luciferase reporter gene (THP-1 LTRluc). The factor is present in the overnight culture fluid and is readily released from the organisms into aqueous medium by vigorous mixing. Staphylococcal extracellular material is a complex mixture of polysaccharide and protein containing peptidoglycan and teichoic acid, released in part by cell wall turnover. The importance of the carbohydrate component is emphasized by concanavalin A (Con A) inhibition of staphylococcal product-induced LTR activation but not of activation by phorbol 12-myristate 13-acetate or tumor necrosis factor. The effect of Con A was decreased or abolished by sugars in the order methyl alpha-D-mannopyranoside > methyl alpha-D-glucopyranoside > mannose > glucose = fructose > N-acetylglucosamine. Wheat germ agglutinin was less inhibitory than Con A; in this instance N-acetylglucosamine decreased inhibition, whereas methyl alpha-D-mannopyranoside or methyl alpha-D-glucopyranoside did not. The induction of luciferase activity in THP-1 LTRluc by the staphylococcal extracellular product also was inhibited by fetal bovine and normal human serum. A comparison of 31 staphylococcal isolates (9 Staphylococcus aureus, 11 Staphylococcus epidermidis, 2 Staphylococcus haemolyticus, 4 Staphylococcus hominis, 2 Staphylococcus capitis, 2 Staphylococcus warneri, 1 Staphylococcus saprophyticus) revealed wide variation in LTR activating activity that did not correlate closely with slime production. Our findings, using induction of luciferase in THP-1 LTRluc as a model for upregulation of HIV infection, raise the possibility that staphylococci, as well as certain other microorganisms, release carbohydrate-containing exopolymers, which can activate the HIV-1 LTR, thus influencing progression of HIV infection.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: S J
authors.initials: SJ
authors.lastname: Klebanoff
authors.forename: F
authors.initials: F
authors.lastname: Kazazi
authors.forename: W C
authors.initials: WC
authors.lastname: Van Voorhis
authors.forename: K G
authors.initials: KG
authors.lastname: Schlechte
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis / Q000378:metabolism; D009005:Monosaccharides / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000302:isolation & purification / Q000494:pharmacology*; D013210:Staphylococcus / Q000302:isolation & purification / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014909:Wheat Germ Agglutinins / Q000494:pharmacology
chemical_list: D009005:Monosaccharides; D011135:Polysaccharides, Bacterial; D014909:Wheat Germ Agglutinins; D003208:Concanavalin A; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate