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Curaxin CBL0137 has the potential to reverse HIV‐1 latency.

Authors :
Jean, Maxime J.
Zhou, Dawei
Fiches, Guillaume
Kong, Weili
Huang, Huachao
Purmal, Andrei
Gurova, Katerina
Santoso, Netty G.
Zhu, Jian
Source :
Journal of Medical Virology; Aug2019, Vol. 91 Issue 8, p1571-1576, 6p
Publication Year :
2019

Abstract

A cure for human immunodeficiency virus type‐1 (HIV‐1) has been hampered by the limitation of current combination antiretroviral therapy (cART) to address the latent reservoirs in HIV‐1 patients. One strategy proposed to eradicate these reservoirs is the "shock and kill" approach, where latency‐reversing agents (LRAs) are used to reactivate and promote viral cell death and/or immune killing of reactivated cells. Here, we report that curaxin CBL0137, an antitumor compound, can potentiate tumor necrosis factor‐α‐mediated reactivation of latently infected HIV‐1cell lines. Additionally, the single use of CBL0137 is sufficient to reactivate HIV‐1 latent reservoirs in peripheral mononuclear cells (PBMCs) isolated from HIV‐1 positive, cART‐treated, aviremic patients. Thus, CBL0137 possesses capabilities as a LRA and could be considered for the "shock and kill" approach. Highlight: The present work identifies the anti‐tumor compound, curaxin CBL0137, as a latency reversing agent (LRA) capable of reactivating HIV‐1 latent reservoirs. Specifically, CBL0137 was able to reactivate latently infected HIV‐1 cell lines in combination with TNFα. Moreover, viral reservoirs isolated from HIV‐1, cART‐treated, aviremic patients were susceptible to induction by CBL0137 alone and in combination with TNFα for one donor. These observations support the use of CBL0137 as a future therapeutic option to address HIV‐1 latency. [ABSTRACT FROM AUTHOR]

Subjects

Subjects :
HIV
CELL death

Details

Language :
English
ISSN :
01466615
Volume :
91
Issue :
8
Database :
Complementary Index
Journal :
Journal of Medical Virology
Publication Type :
Academic Journal
Accession number :
137231475
Full Text :
https://doi.org/10.1002/jmv.25487