SIVs carrying the Q76A Vpx point mutant, which specifically blocks the interaction of Vpx with DCAF1 and the subsequent recruitment of SAMHD1 to the Cullen 4A-ring ubiquitin ligase complex, exhibited an attenuated replication phenotype during infection of ConA activated rhesus macaque PBMC and were deficient in degrading endogenous SAMHD1 in cultured rhesus CD4+ T lymphocytes. Here, DCAF1 is linked to infection.