HIV-1 adaptation to NK-cell-mediated immune pressure

Galit Alter; David Heckerman; Arne Schneidewind; Lena Fadda; Carl M Kadie; Jonathan M Carlson; Cesar Oniangue-Ndza; Maureen Martin; Bin Li; Salim I Khakoo; Mary Carrington; Todd M Allen; Marcus Altfeld

doi:10.1038/nature10237

HIV-1 adaptation to NK-cell-mediated immune pressure

Nature. 2011 Aug 3;476(7358):96-100. doi: 10.1038/nature10237.

Authors

Galit Alter¹, David Heckerman, Arne Schneidewind, Lena Fadda, Carl M Kadie, Jonathan M Carlson, Cesar Oniangue-Ndza, Maureen Martin, Bin Li, Salim I Khakoo, Mary Carrington, Todd M Allen, Marcus Altfeld

Affiliation

¹ Ragon Institute at MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.

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

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adaptation, Physiological / genetics
Adaptation, Physiological / immunology*
Antibodies, Neutralizing / immunology
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / virology
Decision Trees
Evolution, Molecular*
Genotype
HIV Infections / immunology*
HIV Infections / virology*
HIV-1 / genetics
HIV-1 / immunology*
HIV-1 / physiology
Host-Pathogen Interactions / immunology
Human Immunodeficiency Virus Proteins / genetics
Human Immunodeficiency Virus Proteins / immunology
Human Immunodeficiency Virus Proteins / metabolism
Humans
Immune Evasion / immunology*
Killer Cells, Natural / immunology*
Polymorphism, Genetic
Receptors, KIR / deficiency
Receptors, KIR / genetics
Receptors, KIR / immunology
Receptors, KIR / metabolism
Receptors, KIR2DL2 / chemistry
Receptors, KIR2DL2 / deficiency
Receptors, KIR2DL2 / genetics
Receptors, KIR2DL2 / immunology
Viral Regulatory and Accessory Proteins / genetics
Viral Regulatory and Accessory Proteins / immunology
Viral Regulatory and Accessory Proteins / metabolism
Virus Replication
env Gene Products, Human Immunodeficiency Virus / genetics
env Gene Products, Human Immunodeficiency Virus / immunology
env Gene Products, Human Immunodeficiency Virus / metabolism

Substances

Antibodies, Neutralizing
Human Immunodeficiency Virus Proteins
KIR2DL2 protein, human
Receptors, KIR
Receptors, KIR2DL2
Viral Regulatory and Accessory Proteins
env Gene Products, Human Immunodeficiency Virus
vpu protein, Human immunodeficiency virus 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding