Fig. 6
From: PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation
PIM kinase inhibition prevents Vpx-mediated SAMHD1 degradation. a–c PIM kinase inhibitors block HIV-2 infection in primary human monocyte–derived macrophages. Schematic representation of the experimental design (a). Primary monocytes were differentiated into macrophages and infected with HIV-2 reporter virus carrying wild-type Vpx or its S13A mutants. A pan-PIM kinase inhibitor AZD1208 was added 4 h before infection. Forty-eight hours post-infection, cells were harvested and subjected to luciferase assay (b) and immunoblotting (c) to measure HIV-2 infectivity and SAMHD1 expression, respectively. d–f The effect of PIM kinase inhibitors is SAMHD1-dependent. Schematic representation of the experimental procedure (d). Monomac6 (MM6) cells stably expressing shRNAs targeting SAMHD1 were differentiated into macrophages and infected with wild-type HIV-2 reporter virus. AZD1208 (e) or SGI1776 (f) was added 4 h before infection. Forty-eight hours post-infection, cells were harvested and subjected to luciferase assay to measure HIV-2 infectivity. All graphs are presented as a mean ± s.d. (n = 3). **P < 0.01; ***P < 0.001; ns, not significant, two-tailed unpaired t-test. Source data are provided as a Source Data file
