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

Roger Badia, Maria Pujantell, Eva Riveira-Muñoz, Teresa Puig, Javier Torres-Torronteras, Ramón Martí, Bonaventura Clotet, Rosa M. Ampudia, Marta Vives-Pi, José A. Esté, Ester Ballana

Research output: Contribution to journalArticleResearchpeer-review

23 Citations (Scopus)

Abstract

© 2016 Badia et al. 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.
Original languageEnglish
Article numbere1005829
JournalPLoS Pathogens
Volume12
Issue number8
DOIs
Publication statusPublished - 1 Aug 2016

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