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)

• Type of Material: Article
• Authors: Georges Khoury, Emory University; Deanna Kulpa, Emory University; Matthew Parsons, Emory University
• Language: English
• Date: 2021-08-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/v13081451
• Title of Journal or Parent Work: VIRUSES-BASEL
• Volume: 13
• Issue: 8
• Grant/Funding Information: This work was assisted in part by a supplemental grant from the NIH Center for AIDS Research at Emory University (P30AI050409).; This work was also supported by the National Institutes of Health’s Office of the Director, Office of Research Infrastructure Programs (P51OD011132).
• Keywords: RECEPTOR 9 AGONIST; NK CELLS; Virology; Life Sciences & Biomedicine; DEPLETION; EXPRESSION; HISTONE DEACETYLASE INHIBITOR; CD8(+) T cells; ANTIBODY; IMMUNODEFICIENCY-VIRUS-INFECTION; Science & Technology; HIV-1 cure; HIV-1 latency; PLASMA VIREMIA; RHESUS; CD4+ CELLS; NK cells

Abstract

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.