title: HIV Latency-Reversing Agents Have Diverse Effects on Natural Killer Cell Function.
abstract: In an effort to clear persistent HIV infection and achieve a durable therapy-free remission of HIV disease, extensive pre-clinical studies and early pilot clinical trials are underway to develop and test agents that can reverse latent HIV infection and present viral antigen to the immune system for clearance. It is, therefore, critical to understand the impact of latency-reversing agents (LRAs) on the function of immune effectors needed to clear infected cells. We assessed the impact of LRAs on the function of natural killer (NK) cells, the main effector cells of the innate immune system. We studied the effects of three histone deacetylase inhibitors [SAHA or vorinostat (VOR), romidepsin, and panobinostat (PNB)] and two protein kinase C agonists [prostratin (PROST) and ingenol] on the antiviral activity, cytotoxicity, cytokine secretion, phenotype, and viability of primary NK cells. We found thatex vivoexposure to VOR had minimal impact on all parameters assessed, while PNB caused a decrease in NK cell viability, antiviral activity, and cytotoxicity. PROST caused non-specific NK cell activation and, interestingly, improved antiviral activity. Overall, we found that LRAs can alter the function and fate of NK cells, and these effects must be carefully considered as strategies are developed to clear persistent HIV infection.
authors.affiliation: UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Garrido
authors.affiliation: Department of Medicine, University of Utah School of Medicine , Salt Lake City, UT , USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Spivak
authors.affiliation: UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Soriano-Sarabia
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University , Cleveland, OH , USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Checkley
authors.affiliation: Department of Immunology and Microbiology, Rush University Medical Center , Chicago, IL , USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Barker
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University , Cleveland, OH , USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Karn
authors.affiliation: Department of Pathology, University of Utah School of Medicine , Salt Lake City, UT , USA.
authors.forename: Vicente
authors.initials: V
authors.lastname: Planelles
authors.affiliation: UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Margolis
keywords: HIV; immune function; latency reversing agents; natural killer cells