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
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / pharmacology
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Cell Division / drug effects
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Cells, Cultured
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Cytokines / metabolism*
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Gene Products, gag / immunology
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Gene Products, gag / pharmacology*
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HIV Antigens / immunology
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HIV Antigens / pharmacology*
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Humans
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Interferon-gamma / biosynthesis
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Interleukin-12 / metabolism
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Interleukin-12 / pharmacology
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Interleukin-15 / metabolism
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Interleukin-15 / pharmacology
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Interleukin-2 / metabolism
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Interleukin-2 / pharmacology
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Interleukin-4 / pharmacology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism*
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Recombinant Proteins / pharmacology
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Stimulation, Chemical
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Tumor Necrosis Factor-alpha / biosynthesis
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Viral Proteins*
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gag Gene Products, Human Immunodeficiency Virus
Substances
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Antibodies, Monoclonal
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Cytokines
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Gene Products, gag
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HIV Antigens
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Interleukin-15
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Interleukin-2
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Viral Proteins
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gag Gene Products, Human Immunodeficiency Virus
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p17 protein, Human Immunodeficiency Virus Type 1
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Interleukin-12
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Interleukin-4
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Interferon-gamma