title: The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells.
abstract: 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.
authors.affiliation: AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Badia
authors.affiliation: AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Pujantell
authors.affiliation: AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Riveira-Muñoz
authors.affiliation: AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Puig
authors.affiliation: Research Group on Neuromuscular and Mitochondrial Disorders, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, and Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Torres-Torronteras
authors.affiliation: Research Group on Neuromuscular and Mitochondrial Disorders, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, and Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Martí
authors.affiliation: AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Biomedical Network Research Centre on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Ampudia
authors.affiliation: Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Biomedical Network Research Centre on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Marta
authors.identifier: 0000-0003-3735-0779
authors.initials: M
authors.lastname: Vives-Pi
authors.affiliation: AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: José A
authors.identifier: 0000-0002-1436-5823
authors.initials: JA
authors.lastname: Esté
authors.affiliation: AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.|Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Ballana
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D056742:Cyclin D2 / Q000276:immunology*; D051358:Cyclin-Dependent Kinase 4 / Q000276:immunology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000276:immunology; D000076106:SAM Domain and HD Domain-Containing Protein 1
chemical_list: C080336:CCND2 protein, human; C493956:CDKN1A protein, human; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C495900:CDK4 protein, human; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; C484281:Samhd1 protein, mouse; D020559:Monomeric GTP-Binding Proteins