Natural killer cell inhibits human immunodeficiency virus replication in chronically infected immune cells.
Natural killer (NK) cells are a crucial component of the host innate immune system. We investigated the noncytolytic anti-human immunodeficiency virus (HIV) activity of NK cells in chronically HIV-infected immune cells. Supernatants collected from NK cell cultures (both primary NK cells and NK cell lines, YTS and NK 92) inhibited HIV activation in peripheral blood mononuclear cells (PBMCs) from HIV-infected subjects. NK supernatants (NK SN) also suppressed tumor necrosis factor (TNF)-alpha-induced HIV activation in chronically infected cell lines (U1 and ACH-2 cells). The antibody to interferon (IFN)-gamma blocked NK SN-mediated anti-HIV effect, while the antibodies to CC-chemokines had no impact on NK SN-mediated HIV inhibition in U1 and ACH-2 cells. Investigation of mechanism(s) responsible for the NK action showed that NK SN inhibited TNF-alpha-mediated activation of HIV-long-terminal repeat (LTR), and upregulated the expression of signal transducer and activator of transcription (STAT)-1 and phosphorylated P38 mitogen-activated protein kinase (MAPK). The P38 MAPK inhibitor (SB 203580) blocked NK SN-mediated HIV inhibition. These data provide compelling evidence that NK cells have a critical role in controlling HIV activation in the reservoirs.
Zhang
Ting
T
Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute of The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Li
Yuan
Y
Wang
Yan-Jian
YJ
Wang
Xu
X
Young
Mike
M
Douglas
Steven D
SD
Ho
Wen-Zhe
WZ
D006678:HIV / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells; D014779:Virus Replication / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism
D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases