Extended Data Fig. 9: The GFP-SAMHD1 fusion protein, expressed from the SAMHD1 locus, can be degraded by the lentiviral Vpx protein.

Monoclonal SAMHD1 KO cells were generated in human glioblastoma cell line LN18. Next, SAMHD1 KO LN18 cells were stably transfected with linearized plasmids encoding for either GFP-SAMHD1 or SAMHD1-GFP. GFP-positive cells were sorted by flow cytometry 4 weeks after transfection. To deliver Vpx into cells, WT LN18 and SAMHD1 KO cells expressing either GFP-SAMHD1 or SAMHD1-GFP were challenged with VSV- G pseudotyped virus like particles (VLPs) with incorporated lentiviral Vpx (Vpx-VLPs). Empty VLPs (Ø) or VLPs with incorporated Vpr (Vpr-VLPs) were used as negative controls. After VLP treatment, cells were collected and SAMHD1 immunoblots performed. Vinculin served as loading control. Endogenous SAMHD1 in WT cells and stably expressed GFP-SAMHD1 were degraded by Vpx. In contrast, SAMHD1-GFP was protected from Vpx degradation likely due to steric hindrance. Experiment performed only one time.