Human and simian immunodeficiency viruses deregulate early hematopoiesis through a Nef/PPARγ/STAT5 signaling pathway in macaques
J. Clin. Invest. Stéphane Prost, et al. 118:1765 doi:10.1172/JCI33037 [
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Figure 2Nef mimics SIV actions on hematopoietic progenitors. (
A–
C) CFC assays were performed with CD34
+ cells isolated from 3–4 control animals following incubation for 48 hours with (
A) plasma from noninfected animals in the absence (control) or presence of infectious or heat-inactivated SIVmac251 particles (1 × 10
2 particles/ml), (
B) plasma from noninfected animal (control) or plasma from 4 chronically infected macaques without (–) or with (+) Nef immunodepletion, or (
C) with various concentrations of recombinant SIVmac251 Nef. (
D) CFC assays were performed with CD34
+ BM cells isolated from SIVmac251-infected or noninfected macaques. Progenitors from uninfected animals were either left untreated or incubated for 48 hours with the viral isolate SIVmac251, molecular clones BK28-41 (BK) or BK28-41ΔNef (BKΔ) (1 × 10
2 infectious particles/ml), or with rNef (0.15 μM) before being processed for CFC assays. (
E) Inhibitory activity of recombinant myristoylated HIV-1 Nef was assayed on CD34
+ BM cells isolated from 2 healthy macaques. CD34
+ BM cells were preincubated for 48 hours with the indicated concentration of myristoylated HIV-1 Nef before CFC assays. Horizontal lines and the diagonal line in
C indicate mean of CFC numbers scored from all cell cultures from the animals analyzed. Each kind of symbol represents samples from a single animal.