Based on the conclusion from the recent studies with HCMV [16–18], together with the present results, it is our hypothesis that SAMHD1 becomes phosphorylated at pT592 after HCMV infection mainly by Cdk2 and pUL97, leading to a negative regulation of the antiviral activity, possibly through an alteration in the conformation of the enzyme from the tetrameric active form to the monomeric inactive form, an aspect however still highly debated [34,40,43–46,52–53]. Here, CDK2 is linked to cytomegalovirus infection.