The use of cells derived from patients with Aicardi–Goutières syndrome carrying a defect in the SAMHD1 gene2,3 as well as the use of lentiviral Vpx proteins to increase the susceptibility of noncycling cells to HIV-1 infection has led to the identification of SAMHD1 as a critical barrier for reverse transcription of incoming viral genomes3–6. This evidence concerns the gene SAMHD1 and HIV-1 infection.