Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7333
The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
Lopez-Huertas, Maria Rosa ISCIII | Jiménez-Tormo, Laura | Madrid-Elena, Nadia | Gutiérrez, Carolina | Rodríguez-Mora, Sara ISCIII | Coiras, Mayte ISCIII | Alcamí, José ISCIII | Moreno, Santiago
Sci Rep. 2017 May;7(1):2385.
A potential strategy to cure HIV-1 infection is to use latency reversing agents (LRAs) to eliminate latent reservoirs established in resting CD4+ T (rCD4+) cells. As no drug has been shown to be completely effective, finding new drugs and combinations are of increasing importance. We studied the effect of Maraviroc (MVC), a CCR5 antagonist that activates NF-κB, on HIV-1 replication from latency. HIV-1-latency models based on CCL19 or IL7 treatment, before HIV-1 infection were used. Latently infected primary rCD4+ or central memory T cells were stimulated with MVC alone or in combination with Bryostatin-1, a PKC agonist known to reverse HIV-1 latency. MVC 5 μM and 0.31 μM were chosen for further studies although other concentrations of MVC also increased HIV-1 replication. MVC was as efficient as Bryostatin-1 in reactivating X4 and R5-tropic HIV-1. However, the combination of MVC and Bryostatin-1 was antagonistic, probably because Bryostatin-1 reduced CCR5 expression levels. Although HIV-1 reactivation had the same tendency in both latency models, statistical significance was only achieved in IL7-treated cells. These data suggest that MVC should be regarded as a new LRA with potency similar as Bryostatin-1. Further studies are required to describe the synergistic effect of MVC with other LRAs.
Bryostatins | CCR5 Receptor Antagonists | CD4-Positive T-Lymphocytes | Cell Proliferation | Chemokine CCL19 | Gene Expression Regulation | HIV-1 | Humans | Interleukin-7 | Maraviroc | NF-kappa B | Primary Cell Culture | Protein Kinase C | Receptors, CCR5 | Signal Transduction | Virus Latency | Virus Replication | Host-Pathogen Interactions
Files in this item