Potential Utility of Natural Killer Cells for Eliminating Cells Harboring Reactivated Latent HIV-1 Following the Removal of CD8 + T Cell-Mediated Pro-Latency Effect(s)

An impediment to curing HIV-1 infection is the persistence of latently infected cells in ART-treated people living with HIV (PLWH). A key strategy for curing HIV-1 infection is to activate transcription and translation of latent virus using latency reversing agents (LRAs) and eliminate cells harbori...

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Bibliographic Details
Published in:Viruses 2021-07, Vol.13 (8), p.1451
Main Authors: Khoury, Georges, Kulpa, Deanna A, Parsons, Matthew S
Format: Article
Language:English
Subjects:
Animals
Antiretroviral therapy
Apoptosis
CD8 antigen
CD8+ T cells
CD8-Positive T-Lymphocytes - immunology
Clinical trials
Clinical Trials as Topic
Cytokines
DNA methylation
Epigenetics
FDA approval
HIV
HIV Infections - immunology
HIV Infections - virology
HIV-1 - immunology
HIV-1 - physiology
HIV-1 cure
HIV-1 latency
Human immunodeficiency virus
Humans
Immune clearance
Infections
Killer Cells, Natural - immunology
Kinases
Latency
Latent infection
Lymphocytes
Lymphocytes T
Mice
Natural killer cells
NK cells
Proteins
Review
Transcription
Virus Activation - immunology
Virus Latency - immunology
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Summary:An impediment to curing HIV-1 infection is the persistence of latently infected cells in ART-treated people living with HIV (PLWH). A key strategy for curing HIV-1 infection is to activate transcription and translation of latent virus using latency reversing agents (LRAs) and eliminate cells harboring reactivated virus via viral cytopathic effect or immune clearance. In this review, we provide an overview of available LRAs and their use in clinical trials. Furthermore, we describe recent data suggesting that CD8 T cells promote HIV-1 latency in the context of ART, even in the presence of LRAs, which might at least partially explain the clinical inefficiency of previous "shock and kill" trials. Here, we propose a novel cure strategy called "unlock, shock, disarm, and kill". The general premise of this strategy is to shut down the pro-latency function(s) of CD8 T cells, use LRAs to reverse HIV-1 latency, counteract anti-apoptotic molecules, and engage natural killer (NK) cells to mediate the killing of cells harboring reactivated latent HIV-1.
ISSN:1999-4915
1999-4915
DOI:10.3390/v13081451