– Plays a role in nuclear translocation of the viral pre-integration complex (PIC), thus is required for the virus to infect non-dividing cells. Targets specific host proteins for degradation by the 26S proteasome. Acts by associating with the cellular CUL4A-DDB1 E3 ligase complex through direct interaction with host VPRPB/DCAF-1. This change in the E3 ligase substrate specificity results in the degradation of host SAMHD1. In turn, SAMHD1 depletion allows viral replication in host myeloid cells by preventing SAMHD1-mediated hydrolysis of intracellular dNTPs necessary for reverse transcription.