It has recently been reported that the APC bridge subunits APC4 and APC5 are degraded during HCMV infection and the complex dissociates [24] . To test if pUL21a was required for these events, we first examined APC subunit accumulation during infection with or without pUL21a. Levels of APC4 and APC5 proteins were markedly reduced during wild-type infection relative to mock-infected cells at 24 hpi ( Figure 3A ). However, no reduction was observed in APC4 and APC5 levels during infection with the UL21a-deletion virus. The pUL21a-deficient virus fails to express late viral genes due to a defect in viral DNA synthesis [30] . To rule out any role of late genes in APC4 and APC5 degradation, we treated infected cells with phosphonoacetic acid (PAA) to block viral DNA synthesis and late gene expression. APC4 and APC5 levels were reduced during infection with wild-type virus but remained elevated during infection with the UL21a-deletion virus, even following PAA treatment. Furthermore, there was no appreciable difference in APC4 and APC5 transcript levels between wild-type and deletion virus infections ( Figure 3B ). These data suggest that the changes in APC4 and APC5 protein levels occur at the level of protein stability. Consistent with this hypothesis, MG132 enhanced APC4 and APC5 protein levels during infection with wild-type but not deletion virus ( Figure 3C ). Thus, pUL21a-mediated loss of APC4 and APC5 was due to proteasomal degradation. Moreover, the APC binding mutant virus ADpmUL21a PR-AA was unable to degrade APC4 and APC5 while the ADpmUL21a PH-AA virus was as efficient as the wild-type control virus. These data support the conclusion that pUL21a binding to the APC promotes proteasomal degradation of APC4 and APC5.