HIV-1 matrix protein p17 enhances the proliferative activity of natural killer cells and increases their ability to secrete proinflammatory cytokines

Br J Haematol. 2003 Jan;120(2):337-43. doi: 10.1046/j.1365-2141.2003.04053.x.

Abstract

We investigated the effects of human immunodeficiency type-1 virus (HIV-1) matrix protein p17 on freshly isolated and purified human natural killer (NK) cells. HIV-1 p17 increased the cytokines interleukin (IL) 2, IL-12 and IL-15, and induced natural killer cell proliferation, but not cytotoxicity. This effect was specific because it was abrogated by anti-p17 monoclonal antibody. Moreover, HIV-1 p17 enhanced the cytokine-induced production of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma by NK cells. IL-4 downregulated IFN-gamma and TNF-alpha secretion in IL-2- and IL-15-treated NK cells. HIV-1 p17 restored the ability of NK cells to produce both cytokines when added to the cultures simultaneously with IL-4. The property of p17 to increase the production of TNF-alpha and IFN-gamma might be a mechanism used by HIV-1 to modulate the immune system to support its replication and spreading.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Cell Division / drug effects
  • Cells, Cultured
  • Cytokines / metabolism*
  • Gene Products, gag / immunology
  • Gene Products, gag / pharmacology*
  • HIV Antigens / immunology
  • HIV Antigens / pharmacology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / metabolism
  • Interleukin-12 / pharmacology
  • Interleukin-15 / metabolism
  • Interleukin-15 / pharmacology
  • Interleukin-2 / metabolism
  • Interleukin-2 / pharmacology
  • Interleukin-4 / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Recombinant Proteins / pharmacology
  • Stimulation, Chemical
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Viral Proteins*
  • gag Gene Products, Human Immunodeficiency Virus

Substances

  • Antibodies, Monoclonal
  • Cytokines
  • Gene Products, gag
  • HIV Antigens
  • Interleukin-15
  • Interleukin-2
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Viral Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • p17 protein, Human Immunodeficiency Virus Type 1
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma