HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal
Guoxin Wu, Michael Swanson, Aarthi Talla, Donald Graham, Julie Strizki, Daniel Gorman, Richard JO Barnard, Wade Blair, Ole S Sogaard, Martin Tolstrup, Lars Ostergaard, Thomas A Rasmussen, Rafick-Pierre Sekaly, Nancie M Archin, David M Margolis, Daria J Hazuda, Bonnie J Howell
JCI INSIGHT | AMER SOC CLINICAL INVESTIGATION INC | Published : 2017
Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs. Importantly, we demonstrate that clinical admin..View full abstract
Awarded by NIH
Awarded by National Institute Of Mental Health (NIMH) of the National Institutes of Health
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
The authors would like to thank Yanyan Zheng and Laurence Fayadat-Dilman for contributing to thedesign, generation, and characterization of the BsAb reagents. We'd also like to thank the HIV+ patients for donating biological samples to support cure research. Partial research funding was provided by NIH grant U01 AI095052 (to DMM) and The Danish Council for Strategic Research and Aarhus University (to TAR, OSS, MT, and LO). Research reported in this publication was also supported (in part) by CARE, a Martin Delaney Collaboratory, the National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders And Stroke (NINDS), National Institute On Drug Abuse (NIDA) and the National Institute Of Mental Health (NIMH) of the National Institutes of Health, grant number 1UM1AI126619. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.