The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells
Badia, Roger (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Pujantell, Maria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Riveira Muñoz, Eva (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Puig Reixach, Maria Teresa (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Torres Torronteras, Javier (Hospital Universitari Vall d'Hebron)
Martí, Ramon A. (Hospital Universitari Vall d'Hebron)
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ampudia Carrasco, Rosa María (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Vives Pi, Marta (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Este, José (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ballana, Ester (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)

Date:	2016
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.
Grants:	Ministerio de Economía y Competitividad BFU2015-63800-R Ministerio de Economía y Competitividad PI13/01083 Ministerio de Economía y Competitividad PI15/00492 Ministerio de Economía y Competitividad CP14/00016
Note:	Altres ajuts: RETICS/RD12/0017
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	VIH (Virus)
Published in:	PLOS pathogens, Vol. 12 Núm. 8 (August 2016) , ISSN 1553-7374

DOI: 10.1371/journal.ppat.1005829
PMID: 27541004

22 p, 3.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles