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

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)

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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Contributors

Author: Salim I. Khakoo

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