title: HIV-1 adaptation to NK-cell-mediated immune pressure.
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.
authors.affiliation: Ragon Institute at MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Arne
authors.initials: A
authors.lastname: Schneidewind
authors.forename: Lena
authors.initials: L
authors.lastname: Fadda
authors.forename: Carl M
authors.initials: CM
authors.lastname: Kadie
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Carlson
authors.forename: Cesar
authors.initials: C
authors.lastname: Oniangue-Ndza
authors.forename: Maureen
authors.initials: M
authors.lastname: Martin
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Salim I
authors.initials: SI
authors.lastname: Khakoo
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003663:Decision Trees; D019143:Evolution, Molecular; D005838:Genotype; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054343:Receptors, KIR2DL2 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D057134:Antibodies, Neutralizing; D054298:Human Immunodeficiency Virus Proteins; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D054334:Viral Regulatory and Accessory Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C515077:KIR2DL2 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins