Fig. 7
Scheme of SAMHD1’s role in HMA metabolism and effector functions. Metabolic pathway of DAC and AZA.After their cellular uptake by nucleoside-specific transporters, AZA and DAC are activated and metabolically converted into the active nucleotides AZA-TP and DAC-TP, respectively, by sequential phosphorylation events. Importantly, a fraction of the intermediate AZA-DP can be converted to DAC-DP by ribonucleotide reductase (RNR). DAC-TP, but not AZA-TP, can activate and become hydrolyzed by SAMHD1. Strategies to interfere with SAMHD1 expression and function include degradation through Vpx-carrying virus-like particles (Vpx-VLPs), RNA interference or small-molecule inhibitors of SAMHD1’s triphosphohydrolase activity. See also Supplementary Fig. 1 for details, figure created by Dr. Alessia Ruggieri, University of Heidelberg
