The ribonuclease activity of SAMHD1 is required for HIV-1 restriction

Kwangseog Ahn and colleagues show that the RNase activity of SAMHD1 accounts for its ability to limit HIV-1 replication by degrading HIV-1 RNA. The HIV-1 restriction factor SAM domain– and HD domain–containing protein 1 (SAMHD1)1,2 is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool3,4,5. However, phosphorylation of SAMHD1 regulates its ability to restrict HIV-1 without decreasing cellular dNTP levels6,7,8, which is...