Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations

• DOI: 10.1371/journal.ppat.1007991
• Publication Date: 2019-08-19T13:32:24Z
• Authors: Judith Grau-Expósito; Laura Luque-Balle...; Jordi Navarro; Adrian Curran; Joaquin Burgos; Esteban Ribera; Ariadna Torrella; Bibiana Planas; Rosa Badía; Mario Martin-Cast...; Jesús Fernández-Sojo; Meritxell Genescà; Vicenç Falcó; Maria J. Buzon
• Keywords: Panobinostat; Virus latency

Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of latent reservoir antiretroviral treated patients. The capacity LRAs perturb viral present distinct subpopulations cells is currently unknown. Here, using a new RNA FISH/flow ex reactivation assay, we performed comprehensive assessment different families LRAs, and their combinations, CD4+ T cell subsets. We observed that median 16.28% whole HIV-reservoir induced transcripts after reactivation, only 10.10% these RNA+ produced protein p24. Moreover, none were powerful enough reactivate all subpopulations. For instance, combination Romidepsin Ingenol was identified as best drugs increasing proportion cells, most, not all, Importantly, memory stem highly resistant Panobinostat Bryostatin-1 significantly increased number transcribing HIV within this subset. Overall, our results validate use technique assess potency among subsets, manifest intrinsic differences between encompass reservoir, highlight difficulty impact infection with available drugs. Thus, important implications for rational design therapies aimed reversing latency from diverse cellular reservoirs.