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

HIV-1 adaptation to NK-cell-mediated immune pressure
HIV-1 adaptation to NK-cell-mediated immune pressure
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.
immunology, genetics and genomics, virology
0028-0836
96-100
Alter, Galit
2742863e-d5cf-4419-b922-9679afa2bc4b
Heckerman, David
7ecd7080-741f-4980-b7c5-00265d78ec05
Schneidewind, Arne
1c045213-2c84-4be3-8a55-ee5a6042ca6a
Fadda, Lena
aa39ca15-e356-4617-a1b9-4fa7d91e2bec
Kadie, Carl M.
39692ef2-fde8-4d28-8e99-1c570a235295
Carlson, Jonathan M.
8857d204-603d-4757-a6f1-0c1202ae8f8d
Oniangue-Ndza, Cesar
0509ee44-39e9-429c-b27d-83350c29927a
Martin, Maureen
cc48b50a-6ed1-401a-81cb-203555b9ff75
Li, Bin
e208428e-dd63-4ccb-bd1d-66a9ef8b648c
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Carrington, Mary
0fd214c9-4cbc-4719-9d75-9997cd474bd8
Allen, Todd M.
00f65bfb-ee43-412d-90c4-500c86a5d085
Altfeld, Marcus
925a7365-9dcf-45a2-b920-e6c386096ce8
Alter, Galit
2742863e-d5cf-4419-b922-9679afa2bc4b
Heckerman, David
7ecd7080-741f-4980-b7c5-00265d78ec05
Schneidewind, Arne
1c045213-2c84-4be3-8a55-ee5a6042ca6a
Fadda, Lena
aa39ca15-e356-4617-a1b9-4fa7d91e2bec
Kadie, Carl M.
39692ef2-fde8-4d28-8e99-1c570a235295
Carlson, Jonathan M.
8857d204-603d-4757-a6f1-0c1202ae8f8d
Oniangue-Ndza, Cesar
0509ee44-39e9-429c-b27d-83350c29927a
Martin, Maureen
cc48b50a-6ed1-401a-81cb-203555b9ff75
Li, Bin
e208428e-dd63-4ccb-bd1d-66a9ef8b648c
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Carrington, Mary
0fd214c9-4cbc-4719-9d75-9997cd474bd8
Allen, Todd M.
00f65bfb-ee43-412d-90c4-500c86a5d085
Altfeld, Marcus
925a7365-9dcf-45a2-b920-e6c386096ce8

Alter, Galit, Heckerman, David, Schneidewind, Arne, Fadda, Lena, Kadie, Carl M., Carlson, Jonathan M., Oniangue-Ndza, Cesar, Martin, Maureen, Li, Bin, Khakoo, Salim I., Carrington, Mary, Allen, Todd M. and Altfeld, Marcus (2011) HIV-1 adaptation to NK-cell-mediated immune pressure. Nature, 476 (7358), 96-100. (doi:10.1038/nature10237). (PMID:21814282)

Record type: Article

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.

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Published date: 3 August 2011
Keywords: immunology, genetics and genomics, virology
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 336170
URI: https://eprints.soton.ac.uk/id/eprint/336170
ISSN: 0028-0836
PURE UUID: 8accfac9-c407-49e0-9bb9-8ea1735cbedb

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Date deposited: 16 Mar 2012 11:44
Last modified: 16 Jul 2019 22:09

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Contributors

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

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