To determine the functional consequence of pUL21a-dependent APC dissociation, we first analyzed the accumulation of APC substrates during wild-type or UL21a-deletion virus infection. The protein levels of APC substrates Cdh1 (that is also an APC coactivator) and geminin were markedly increased in wild-type virus infection as previously reported [27, 33] ( Figure 4A ). However, their levels were reduced during infection with the UL21a-deletion virus, suggesting increased APC activity. The geminin transcript accumulated to wild-type levels even without pUL21a, providing evidence that the difference in protein accumulation was not due to transcriptional regulation ( Figure 4B ). PAA treatment had no effect on substrate accumulation, ruling out pUL21a-mediated late gene expression as the source of the observed phenotype ( Figure  S5A ). MG132 largely restored substrate levels during UL21a deletion viral infection, indicating that the difference is likely due to increased proteasome degradation ( Figure 4C ). These results were also recapitulated during infection of APC binding mutant virus ADpmUL21a PR-AA and its control virus ADpmUL21a PH-AA ( Figure 4C ).