Abstract
Natural killer (NK) cells have an important role in the control of viral infections, recognizing virally infected cells through a variety of activating and inhibitory receptors. Epidemiological and functional studies have recently suggested that NK cells can also contribute to the control of HIV-1 infection through recognition of virally infected cells by both activating and inhibitory killer immunoglobulin-like receptors (KIRs). However, it remains unknown whether NK cells can directly mediate antiviral immune pressure in vivo in humans. Here we describe KIR-associated amino-acid polymorphisms in the HIV-1 sequence of chronically infected individuals, on a population level. We show that these KIR-associated HIV-1 sequence polymorphisms can enhance the binding of inhibitory KIRs to HIV-1-infected CD4(+) T cells, and reduce the antiviral activity of KIR-positive NK cells. These data demonstrate that KIR-positive NK cells can place immunological pressure on HIV-1, and that the virus can evade such NK-cell-mediated immune pressure by selecting for sequence polymorphisms, as was previously described for virus-specific T cells and neutralizing antibodies. NK cells might therefore have a previously underappreciated role in contributing to viral evolution.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Physiological / genetics
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Adaptation, Physiological / immunology*
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Antibodies, Neutralizing / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / virology
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Decision Trees
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Evolution, Molecular*
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Genotype
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HIV Infections / immunology*
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HIV Infections / virology*
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HIV-1 / genetics
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HIV-1 / immunology*
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HIV-1 / physiology
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Host-Pathogen Interactions / immunology
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Human Immunodeficiency Virus Proteins / genetics
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Human Immunodeficiency Virus Proteins / immunology
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Human Immunodeficiency Virus Proteins / metabolism
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Humans
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Immune Evasion / immunology*
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Killer Cells, Natural / immunology*
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Polymorphism, Genetic
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Receptors, KIR / deficiency
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Receptors, KIR / genetics
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Receptors, KIR / immunology
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Receptors, KIR / metabolism
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Receptors, KIR2DL2 / chemistry
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Receptors, KIR2DL2 / deficiency
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Receptors, KIR2DL2 / genetics
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Receptors, KIR2DL2 / immunology
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Viral Regulatory and Accessory Proteins / genetics
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Viral Regulatory and Accessory Proteins / immunology
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Viral Regulatory and Accessory Proteins / metabolism
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Virus Replication
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env Gene Products, Human Immunodeficiency Virus / genetics
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env Gene Products, Human Immunodeficiency Virus / immunology
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env Gene Products, Human Immunodeficiency Virus / metabolism
Substances
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Antibodies, Neutralizing
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Human Immunodeficiency Virus Proteins
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KIR2DL2 protein, human
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Receptors, KIR
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Receptors, KIR2DL2
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Viral Regulatory and Accessory Proteins
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env Gene Products, Human Immunodeficiency Virus
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vpu protein, Human immunodeficiency virus 1