Abstract

Despite efficient virological suppression on antiretroviral therapy (ART), people living with HIV (PLWH), experience an increased burden of premature co-morbidities, such as cancer and end-organ disease. With remaining challenges in terms of access to therapy, adherence and potential long-term drug toxicity, improving their long-term healthcare outcome, including new strategies for HIV clearance, remains a global priority. There is, therefore, an ongoing need to better characterize and harness the immune response in order to develop new strategies and supplement current therapeutic approaches for a “functional” cure. Current efforts toward HIV eradication to enhance immune recognition and elimination of persistently infected cells have highlighted the need for an optimized “kill” approach. Natural killer (NK) cells play an important role in antiviral defense and by virtue of their innate and adaptive features hold great promise as a focus of “kill” efforts. Galvanized by advances in the cancer field, NK cell exploitation, represents a transformative approach to augment HIV therapeutic modalities, circumventing many of the limitations inherent to T cell approaches. In this review we will discuss recent advances in our understanding of the development of NK cell adaptive/memory responses in HIV infection and highlight new and exciting opportunities to exploit the beneficial attributes of NK cells for HIV immunotherapy.

Highlights

  • Reviewed by: Carolina Garrido, The University of North Carolina at Chapel Hill, United States Namal P

  • We have previously demonstrated the rheostat role of Natural killer (NK) cells in human chronic viral infections, with the capacity to restrain antiviral immunity in chronic HBV infection (Peppa et al, 2013), and more recently the ability to regulate the development of broadly neutralizing antibodies in human immunodeficiency virus (HIV) infection (Bradley et al, 2018)

  • This dynamic balance ensures self-tolerance, whilst permitting robust responses against virally infected cells that have downregulated major histocompatibility complex class I (MHC I) molecules that ligate NK-expressed inhibitory receptors, such as killer immunoglobulin-like receptors (KIRs) and CD94/NKG2A, and/or upregulated stress ligands or viral associated molecules recognized by activating receptors, such as NKG2D or natural cytotoxicity receptors (NCRs) (Lanier, 2008; Orr and Lanier, 2010)

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Summary

Introduction

Reviewed by: Carolina Garrido, The University of North Carolina at Chapel Hill, United States Namal P. In this review we will discuss recent advances in our understanding of the development of NK cell adaptive/memory responses in HIV infection and highlight new and exciting opportunities to exploit the beneficial attributes of NK cells for HIV immunotherapy.

Results
Conclusion
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