Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/101495
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Type: Journal article
Title: Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells
Author: 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.
Citation: Journal of NeuroVirology, 2016; 22(4):455-463
Publisher: Springer
Issue Date: 2016
ISSN: 1355-0284
1538-2443
Statement of
Responsibility: 
Lachlan R. Gray, Hung On, Emma Roberts, Hao K. Lu, Michael A. Moso, Jacqueline A. Raison, Catherine Papaioannou, Wan-Jung Cheng, Anne M. Ellett, Jonathan C. Jacobson, Damian F.J. Purcell, Steve L. Wesselingh, Paul R. Gorry, Sharon R. Lewin, Melissa J. Churchill
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.
Keywords: HIV-1; CNS; reservoirs; latency; latency-reversing agents; toxicity
Rights: © Journal of NeuroVirology, Inc. 2016
RMID: 0030042582
DOI: 10.1007/s13365-015-0413-4
Grant ID: http://purl.org/au-research/grants/nhmrc/1051093
http://purl.org/au-research/grants/nhmrc/606967
http://purl.org/au-research/grants/arc/FT120100389
Appears in Collections:Medicine publications

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