To further investigate the mechanism by which SAMHD1 is lost during HCMV infection, we compared the effects of MG132, MLN4924, and bafilomycin A1, a specific and potent inhibitor of vacuolar-type H+-ATPases that blocks lysosomal degradation, on CRL-mediated SAMHD1 loss. Here, IL31RA is linked to cytomegalovirus infection.