Intriguingly, early events in human immunodeficiency virus 1 (HIV-1) infection including uncoating, the liberation of the viral genome, as well as reverse transcription are vulnerable targets for restriction factors such as members of the APOBEC3 family, TRIM5α and TRIMCyp, and the recently identified sterile alpha motif (SAM) and HD domain containing 1 (SAMHD1), a dNTPase that inhibits HIV-1 in differentiated myeloid cells, as well as resting CD4+ T-cells [1-9]. Here, SAMHD1 is linked to HIV-1 infection.