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Evaluation of the innate immune modulator acitretin as a strategy to clear the HIV reservoir.

Evaluation of the innate immune modulator acitretin as a strategy to clear the HIV reservoir.
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Garcia-Vidal E, Castellví M, Pujantell M, Badia R, Jou A, Gomez L, Puig T, Clotet B, Ballana E, Riveira-Muñoz E, Esté JA,


Garcia-Vidal E, Castellví M, Pujantell M, Badia R, Jou A, Gomez L, Puig T, Clotet B, Ballana E, Riveira-Muñoz E, Esté JA, (click to view)

Garcia-Vidal E, Castellví M, Pujantell M, Badia R, Jou A, Gomez L, Puig T, Clotet B, Ballana E, Riveira-Muñoz E, Esté JA,

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Antimicrobial agents and chemotherapy 2017 09 05() pii 10.1128/AAC.01368-17

Abstract

The persistence of HIV despite suppressive antiretroviral therapy is a major roadblock to HIV eradication. Current strategies focused on inducing the expression of latent HIV fail to clear the persistent reservoir, prompting the development of new approaches for killing HIV+ cells. Recently, acitretin has been proposed as a pharmacological innate cellular-defense network enhancer that led to virus reactivation and preferential death of infected cells. We have evaluated the capacity of acitretin to reactivate and/or facilitate immune-mediated clearance of HIV+ cells. Acitretin did not induce HIV reactivation in latently-infected cell lines (J-Lat or ACH-2). We could only observe a modest induction of HIV reactivation by acitretin in latent GFP-HIV Jurkat cells, comparable to suboptimal concentrations of vorinostat a known latency-reversing agent (LRA). However, acitretin induction was insignificant when compared to LRAs optimal concentrations. Acitretin failed to reactivate HIV in a model of latently infected primary CD4+ T-cells but induced RIG-I and MAVS expression in infected and uninfected cells, confirming the role of acitretin as an innate immune modulator. However, this effect was not associated with selective killing of HIV+ cells. In conclusion, acitretin-mediated stimulation of the RIG-I pathway over HIV reactivation is modest and thus may not meaningfully impact the HIV reservoir. Stimulation of the RIG-I-dependent IFN cascade by acitretin may not significantly affect the selective destruction of HIV+ latently infected cells.

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