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

Article

关键词: IMMUNODEFICIENCY-VIRUS TYPE-1;    NATURAL-KILLER-CELLS;    MHC CLASS-I;    HLA-B;    INHIBITORY RECEPTOR;    VIRAL PEPTIDES;    BINDING-SITE;    RECOGNITION;    KIR3DL1;    RESPONSES;   

DOI  :  10.1038/nature10237

来源: SCIE

【 摘 要 】

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(1-3). 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)(4-7). 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(8). NK cells might therefore have a previously underappreciated role in contributing to viral evolution.

【 授权许可】

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