Journal
EBIOMEDICINE
Volume 23, Issue -, Pages 52-58Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2017.07.019
Keywords
HIV; Latency; Eradication; Vorinostat; Immune effector
Funding
- National Institutes of Health [U19-AI096113, UM1AI126619]
- Collaboratory of AIDS Researchers for Eradication [R01 HL132791, KL2 TR001109]
- Cancer Center Core Support Grant [P30 CA016086]
- UNC CFAR [P30 AI504100]
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Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA). The LCA is a quantitative viral outgrowth assay (QVOA) that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus from VOR exposed resting CD4 T cells following addition of immune effectors for a discrete period. Take home message: VOR exposure leads to sufficient production of viral protein on the cell surface, creating a window of vulnerability within this latent reservoir in antiretroviral therapy (ART)-suppressed HIV-infected individuals that allows the clearance of latently infected cells by an array of effector mechanisms. (C) 2017 The Authors. Published by Elsevier B.V.
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