ACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS LONG TERMINAL REPEAT IN THP-1 CELLS BY A STAPHYLOCOCCAL EXTRACELLULAR PRODUCT

Staphylococcal strains can release a factor that strongly activates th e human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LT R) in THP-1 cells transfected with the HIV 1 LTR-driven luciferase rep orter gene (THP-1 LTR(luc)). The factor is present in the overnight cu lture fluid and is readily released from the organisms into aqueous me dium by vigorous mixing. Staphylococcal extracellular material is a co mplex mixture of polysaccharide and protein containing peptidoglycan a nd teichoic acid, released in part by cell wall turnover. The importan ce of the carbohydrate com ponent is emphasized by concanavalin A (Con A) inhibition of staphylococcal product-induced LTR activation but no t of activation by phorbol 12-myristate 13-acetate or tumor necrosis f actor. 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 aggl utinin was less inhibitory than Con A; in this instance N-acetylglucos amine decreased inhibition, whereas methyl alpha-D-mannopyranoside or methyl alpha-D-glucopyranoside did not. The induction of luciferase ac tivity in THP-1 LTR(luc) by the staphylococcal extracellular product a lso was inhibited by fetal bovine and normal human serum. A comparison of 31 staphylococcal isolates (9 Staphylococcus aureus, 11 Staphyloco ccus epidermidis, 2 Staphylococcus haemolyticus, 4 Staphylococcus homi nis, 2 Staphylococcus capitis, 2 Staphylococcus warneri, 1 Staphylococ cus saprophyticus) revealed wide variation in LTR activating activity that did not correlate closely with slime production. Our findings, us ing induction of luciferase in THP-1 LTR(luc) as a model for upregulat ion of HIV infection, raise the possibility that staphylococci, as wel l as certain other microorganisms, release carbohydrate-containing exo polymers, which can activate the HIV-1 LTR, thus influencing progressi on of HIV infection.