The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1

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 eff...

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Autores: Lopez-Huertas, Maria Rosa, Jiménez-Tormo, Laura, Madrid-Elena, Nadia, Gutiérrez, Carolina, Rodríguez-Mora, Sara, Coiras, Mayte, Alcamí, José, Moreno, Santiago
Formato: artículo
Fecha de publicación:2017
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7333
Acesso em linha:http://hdl.handle.net/20.500.12105/7333
Access Level:acceso abierto
Palavra-chave:HIV cure
LRA
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
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spelling The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1Lopez-Huertas, Maria RosaJiménez-Tormo, LauraMadrid-Elena, NadiaGutiérrez, CarolinaRodríguez-Mora, SaraCoiras, MayteAlcamí, JoséMoreno, SantiagoHIV cureLRABryostatinsCCR5 Receptor AntagonistsCD4-Positive T-LymphocytesCell ProliferationChemokine CCL19Gene Expression RegulationHIV-1HumansInterleukin-7MaravirocNF-kappa BPrimary Cell CultureProtein Kinase CReceptors, CCR5Signal TransductionVirus LatencyVirus ReplicationHost-Pathogen InteractionsA 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.Nature Publishing Group20192019-03-1420172017-03-0120172017-03-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/7333reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/73332026-06-12T12:43:37Z
dc.title.none.fl_str_mv The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
title The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
spellingShingle The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
Lopez-Huertas, Maria Rosa
HIV cure
LRA
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
title_short The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
title_full The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
title_fullStr The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
title_full_unstemmed The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
title_sort The CCR5-antagonist Maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1
dc.creator.none.fl_str_mv Lopez-Huertas, Maria Rosa
Jiménez-Tormo, Laura
Madrid-Elena, Nadia
Gutiérrez, Carolina
Rodríguez-Mora, Sara
Coiras, Mayte
Alcamí, José
Moreno, Santiago
author Lopez-Huertas, Maria Rosa
author_facet Lopez-Huertas, Maria Rosa
Jiménez-Tormo, Laura
Madrid-Elena, Nadia
Gutiérrez, Carolina
Rodríguez-Mora, Sara
Coiras, Mayte
Alcamí, José
Moreno, Santiago
author_role author
author2 Jiménez-Tormo, Laura
Madrid-Elena, Nadia
Gutiérrez, Carolina
Rodríguez-Mora, Sara
Coiras, Mayte
Alcamí, José
Moreno, Santiago
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv HIV cure
LRA
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
topic HIV cure
LRA
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
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-03-01
2017
2017-03-01
2019
2019-03-14
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/7333
url http://hdl.handle.net/20.500.12105/7333
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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