Abstract
Natural killer (NK) cells play a critical role in viral immunity. In the setting of HIV infection, epidemiologic and functional evidence support a role for NK cells in both protection from new infection and in viral control. Specifically, NK cells directly mediate immune pressure leading to virus evolution, and NK cell receptor genotypic profiles, clonal repertoires, and functional capacity have all been implicated in virus containment. In addition, indirect NK cell-mediated antibody-dependent cellular cytotoxicity has been linked to vaccine-induced protective immunity against HIV infection. With recent advances in our understanding of NK cell deficiency, development, memory-like responses, and editing of the adaptive immune system, the opportunities to direct and exploit NK cell antiviral immunity to target HIV have exponentially grown. In this review, we seek to highlight the intersections between discoveries in basic NK cell biology and the challenges of HIV chronic infection, vaccine development, and cure/eradication strategies.
Highlights
Natural killer (NK) cells occupy a unique niche in the immune response, bridging the innate and adaptive immune systems
Initiation of therapy changes immunoregulatory markers; modulation of galectin 9 and T cell immunoglobulin and mucin-domain containing molecule-3 (TIM-3) in early infection leads to enhanced NK cell activity, but in chronic HIV the interaction may contribute to NK cell dysfunction [46]
Given the defects seen in chronic HIV infection, understanding key differentiation signals in NK cell biology may point to therapeutic strategies to shape or direct their responses
Summary
Natural killer (NK) cells occupy a unique niche in the immune response, bridging the innate and adaptive immune systems. The HLA/KIR interactions directed by specific HIV-derived peptides are further linked to measures of NK cell function in vitro and patterns of viral escape in population studies [25, 26]. ADCC activity was associated with the modest protective efficacy in the RV144 HIV vaccine trial [6] and has been implicated in phenotypes of viral control [32, 33].
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