Activation of the human immunodeficiency virus long terminal repeat in THP-1 cells by a staphylococcal extracellular product

Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10615-9. doi: 10.1073/pnas.91.22.10615.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cell Line
  • Concanavalin A / pharmacology
  • HIV Long Terminal Repeat / drug effects*
  • HIV-1 / genetics*
  • Humans
  • Kinetics
  • Luciferases / biosynthesis
  • Luciferases / metabolism
  • Monosaccharides / pharmacology
  • Polysaccharides, Bacterial / isolation & purification
  • Polysaccharides, Bacterial / pharmacology*
  • Staphylococcus / isolation & purification
  • Staphylococcus / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection
  • Tumor Cells, Cultured
  • Wheat Germ Agglutinins / pharmacology

Substances

  • Monosaccharides
  • Polysaccharides, Bacterial
  • Wheat Germ Agglutinins
  • Concanavalin A
  • Luciferases
  • Tetradecanoylphorbol Acetate