Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa

选择 HLA-C*03:04 限制性 HIV-1 p24 Gag 序列变体与病毒从 KIR2DL3+ 自然杀伤细胞逃逸有关:来自南非观察队列的数据

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作者:Angelique Hölzemer, Christina F Thobakgale, Camilo A Jimenez Cruz, Wilfredo F Garcia-Beltran, Jonathan M Carlson, Nienke H van Teijlingen, Jaclyn K Mann, Manjeetha Jaggernath, Seung-gu Kang, Christian Körner, Amy W Chung, Jamie L Schafer, David T Evans, Galit Alter, Bruce D Walker, Philip J Goulder,

Background

Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure.

Conclusions

These data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades NK-cell-mediated immune pressure and the functional validation of a structural modeling approach will facilitate the development of novel targeted immune interventions to harness the antiviral activities of NK cells.

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