Fig. 7

Models of how SAMHD1 variants affect dNTP levels and HIV-1 restriction. A A schematic depicting relative dNTP levels in cells expressing different variants of SAMHD1. The graph depicts combined data from our dNTP assays in U937 cells together with projected levels below the assay level of detection. Red lines indicate the thresholds for reverse transcription of WT and Q151N RT mutant HIV-1. Purple line show the limit of detection of the dNTP assay. B A schematic model demonstrating the relationship between virus restriction, SAMHD1 stability and HIV-1 RT efficiency. In cycling cells (left, green quadrants), with high basal dNTP levels, SAMHD1 is unable to restrict viral replication of WT HIV-1 (open symbols) with a highly efficient RT, regardless of tetramer stability. By contrast when HIV RT is made less efficient through the introduction of Q151N mutant (black symbols), both stable and unstable tetramer mutant SAMHD1 can now restrict. In differentiated cells (right, purple quadrants), where the dNTP levels are already reduced, WT and stable SAMHD1 tetramer mutants restrict HIV-1, but tetramer destabilising mutants cannot. Restriction is restored against the RT deficient Q151N virus with stable tetramer SAMHD1 reducing replication to even lower levels