Several restriction factors have been identified that inhibit human immunodeficiency virus (HIV) infection, including APOBEC3G [2], BST2/tetherin and SAMHD1 [3], which block discrete steps of viral replication, such as reverse transcription (APOBEC3G and SAMHD1) or the release of progeny particles from infected cells (tetherin). Here, SAMHD1 is linked to HIV infectious disease.