The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
| Autor: | Nadia Madrid-Elena, Carolina Gutierrez, José Alcamí, Mayte Coiras, Santiago Moreno, Laura Jiménez-Tormo, María Rosa López-Huertas, Sara Rodríguez-Mora |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Agonist CD4-Positive T-Lymphocytes Bryostatin 1 Receptors CCR5 medicine.drug_class Science Primary Cell Culture CCR5 receptor antagonist Pharmacology Biology Virus Replication Article Human herpesvirus-7 encephalitis Maraviroc 03 medical and health sciences chemistry.chemical_compound medicine Potency Humans Latency (engineering) Receptor Protein kinase C Protein Kinase C Cell Proliferation Multidisciplinary Interleukin-7 NF-kappa B virus diseases Immunocompetent adults Bryostatins Virus Latency body regions 030104 developmental biology chemistry Gene Expression Regulation Immunology CCR5 Receptor Antagonists Host-Pathogen Interactions HIV-1 Chemokine CCL19 Medicine Clinical significance HHV-7 CNS human activities Signal Transduction |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) Scientific Reports Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Repisalud Instituto de Salud Carlos III (ISCIII) |
| ISSN: | 2045-2322 |
| Popis: | 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. The authors would like to acknowledge the staff at the Institute of Health Carlos III (National Centre for Microbiology, Madrid, Spain) for their support. No |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |