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

Online publication: 05/09/2017 Journal: Antimicrobial Agents and Chemotherapy

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.

Authors: Edurne Garcia-Vidal, Marc Castellví, Maria Pujantell, Roger Badia, Antoni Jou, Lucia Gomez, Teresa Puig, Bonaventura Clotet, Ester Ballana, Eva Riveira-Muñoz, and José A. Esté.

Subscribe to our newsletter

Back to Top
Irsi Caixa

Promoted by:

'La Caixa' Foundation Generalitat de Catalunya - Departament de Salut

 

HR Excellence in Research

Member of:

Cerca

In cooperation with: