EMBO J 32 18, 2454–2462 doi:; DOI: 10.1038/emboj.2013.163; published online July 19 2013
SAMHD1, a dNTP hydrolase mutated in the autoimmune encephalopathy Aicardi-Goutières syndrome, restricts HIV replication in non-dividing human cells by reducing intracellular deoxyribonucleotide pools. New work in The EMBO Journal unexpectedly finds neither autoimmune disease nor increased murine retrovirus infection in SAMHD1 knockout mice, but improved replication of a mutant HIV with increased sensitivity to low dNTP levels. Thus, while the new mouse model partially recapitulates known features of human SAMHD1, it represents a unique tool to study the role of dNTP regulation during inflammation, viral infection and other pathologies.