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 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. © 2016 badia et al.