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The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells

Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiate...

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Autores principales: Badia, Roger, Pujantell, Maria, Riveira-Muñoz, Eva, Puig, Teresa, Torres-Torronteras, Javier, Martí, Ramón, Clotet, Bonaventura, Ampudia, Rosa M., Vives-Pi, Marta, Esté, José A., Ballana, Ester
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991798/
https://www.ncbi.nlm.nih.gov/pubmed/27541004
http://dx.doi.org/10.1371/journal.ppat.1005829
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author Badia, Roger
Pujantell, Maria
Riveira-Muñoz, Eva
Puig, Teresa
Torres-Torronteras, Javier
Martí, Ramón
Clotet, Bonaventura
Ampudia, Rosa M.
Vives-Pi, Marta
Esté, José A.
Ballana, Ester
author_facet Badia, Roger
Pujantell, Maria
Riveira-Muñoz, Eva
Puig, Teresa
Torres-Torronteras, Javier
Martí, Ramón
Clotet, Bonaventura
Ampudia, Rosa M.
Vives-Pi, Marta
Esté, José A.
Ballana, Ester
author_sort Badia, Roger
collection PubMed
description Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages.
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spelling pubmed-49917982016-09-12 The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells Badia, Roger Pujantell, Maria Riveira-Muñoz, Eva Puig, Teresa Torres-Torronteras, Javier Martí, Ramón Clotet, Bonaventura Ampudia, Rosa M. Vives-Pi, Marta Esté, José A. Ballana, Ester PLoS Pathog Research Article Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. Public Library of Science 2016-08-19 /pmc/articles/PMC4991798/ /pubmed/27541004 http://dx.doi.org/10.1371/journal.ppat.1005829 Text en © 2016 Badia et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Badia, Roger
Pujantell, Maria
Riveira-Muñoz, Eva
Puig, Teresa
Torres-Torronteras, Javier
Martí, Ramón
Clotet, Bonaventura
Ampudia, Rosa M.
Vives-Pi, Marta
Esté, José A.
Ballana, Ester
The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells
title The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells
title_full The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells
title_fullStr The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells
title_full_unstemmed The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells
title_short The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells
title_sort g1/s specific cyclin d2 is a regulator of hiv-1 restriction in non-proliferating cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991798/
https://www.ncbi.nlm.nih.gov/pubmed/27541004
http://dx.doi.org/10.1371/journal.ppat.1005829
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