Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells

Gray, L, On, H, Roberts, E, Lu, H, Moso, M, Raison, J, Papaioannou, C, Cheng, W, Ellett, A, Jacobson, J, Purcell, D, Wesselingh, S, Gorry, P, Lewin, S and Churchill, M 2016, 'Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells', Journal of NeuroVirology, vol. 22, no. 4, pp. 455-463.


Document type: Journal Article
Collection: Journal Articles

Title Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells
Author(s) Gray, L
On, H
Roberts, E
Lu, H
Moso, M
Raison, J
Papaioannou, C
Cheng, W
Ellett, A
Jacobson, J
Purcell, D
Wesselingh, S
Gorry, P
Lewin, S
Churchill, M
Year 2016
Journal name Journal of NeuroVirology
Volume number 22
Issue number 4
Start page 455
End page 463
Total pages 9
Publisher Springer
Abstract Despite the success of combination antiretroviral therapy (cART), HIV persists in long lived latently infected cells in the blood and tissue, and treatment is required lifelong. Recent clinical studies have trialed latency-reversing agents (LRA) as a method to eliminate latently infected cells; however, the effects of LRA on the central nervous system (CNS), a well-known site of virus persistence on cART, are unknown. In this study, we evaluated the toxicity and potency of a panel of commonly used and well-known LRA (panobinostat, romidepsin, vorinostat, chaetocin, disulfiram, hexamethylene bisacetamide [HMBA], and JQ-1) in primary fetal astrocytes (PFA) as well as monocyte-derived macrophages as a cellular model for brain perivascular macrophages. We show that most LRA are non-toxic in these cells at therapeutic concentrations. Additionally, romidepsin, JQ-1, and panobinostat were the most potent at inducing viral transcription, with greater magnitude observed in PFA. In contrast, vorinostat, chaetocin, disulfiram, and HMBA all demonstrated little or no induction of viral transcription. Together, these data suggest that some LRA could potentially activate transcription in latently infected cells in the CNS. We recommend that future trials of LRA also examine the effects of these agents on the CNS via examination of cerebrospinal fluid.
Subject Medical Virology
Keyword(s) CNS
HIV-1
Latency
Latency-reversing agents
Reservoirs
Toxicity
DOI - identifier 10.1007/s13365-015-0413-4
Copyright notice © Journal of NeuroVirology, Inc. 2016
ISSN 1355-0284
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