HIV-1 p17 matrix protein interacts with heparan sulfate side chain of CD44v3, syndecan-2, and syndecan-4 proteoglycans expressed on human activated CD4+ T cells affecting tumor necrosis factor alpha and interleukin 2 production

J Biol Chem. 2011 Jun 3;286(22):19541-8. doi: 10.1074/jbc.M110.191270. Epub 2011 Apr 11.

Abstract

HIV-1 p17 contains C- and N-terminal sequences with positively charged residues and a consensus cluster for heparin binding. We have previously demonstrated by affinity chromatography that HIV-1 p17 binds strongly to heparin-agarose at physiological pH and to human activated CD4(+) T cells. In this study we demonstrated that the viral protein binds to heparan sulfate side chains of syndecan-2, syndecan-4, and CD44v3 purified from HeLa cells and that these heparan sulfate proteoglycans (HSPGs) co-localize with HIV-1 p17 on activated human CD4(+) T cells by confocal fluorescence analysis. Moreover, we observed a stimulatory or inhibitory activity when CD4(+) T cells were activated with mitogens together with nanomolar or micromolar concentrations of the matrix protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Female
  • HIV Antigens / genetics
  • HIV Antigens / immunology
  • HIV Antigens / metabolism*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / metabolism*
  • HeLa Cells
  • Heparitin Sulfate / genetics
  • Heparitin Sulfate / immunology
  • Heparitin Sulfate / metabolism*
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / immunology
  • Hyaluronan Receptors / metabolism*
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Lymphocyte Activation
  • Male
  • Protein Binding
  • Syndecan-2 / genetics
  • Syndecan-2 / immunology
  • Syndecan-2 / metabolism*
  • Syndecan-4 / genetics
  • Syndecan-4 / immunology
  • Syndecan-4 / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • CD44V3,8-10
  • HIV Antigens
  • Hyaluronan Receptors
  • IL2 protein, human
  • Interleukin-2
  • SDC2 protein, human
  • SDC4 protein, human
  • Syndecan-4
  • Tumor Necrosis Factor-alpha
  • gag Gene Products, Human Immunodeficiency Virus
  • p17 protein, Human Immunodeficiency Virus Type 1
  • Syndecan-2
  • Heparitin Sulfate