Combined relief of antiviral restrictions allows efficient transduction of quiescent HSPC
(A) Human MDM (hMDM) were transduced with a Vpx incorporating LV, at MOI of 1. Percentages of transduced cells were assessed at 5 days post-transduction by fluorescence-activated cell sorting (FACS) (mean ± SEM; n = 8; Mann Whitney test). (B) Stimulated (Stim) and unstimulated (Unst) human HSPC (hHSPC) were transduced with LV ± Vpx (MOI = 1 for stimulated; MOI = 5 for unstimulated). Percentages of transduced cells were assessed at 5 days post-transduction by FACS and expressed as fold increase vs. Vpx-control (mean ± SEM; n = 4 stimulated hHSPC; n = 6 unstimulated hHSPC; Wilcoxon signed rank test vs. Vpx- = 1). (C) Transduction efficiencies (MOI = 25) in unstimulated hHSPC ± Vpx ±8 μM CsH (mean ± SEM; n = 6; Mann Whitney test). (D) Transduction efficiencies in the different subpopulations of unstimulated hHSPC expressed as fold increase vs. DMSO control (mean ± SEM; n = 6; Dunn’s adjusted Kruskal-Wallis test vs. DMSO = 1). (E) The composition of unstimulated hHSPC was evaluated 5 days post transduction by FACS (mean ± SEM; n = 5). Statistical significance is for ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001; ns indicates non-significance.