As APC8 was co-immunoprecipitated with pUL21a in our original screen, it raised the possibility that pUL21a might require APC8 to target APC4 and APC5. For instance, pUL21a might bind to APC8 to disrupt the structure of the APC leading to APC4 and APC5 degradation, or it might use APC8 as a docking site for recruiting protein degradation enzymes to target APC4 and APC5. To test this, we depleted APC8 in these cells by shRNA knockdown ( Figure S4 ). Following shRNA depletion of APC8, the APC4 and APC5 levels remained reduced in cells infected with wild-type virus compared to those with UL21a-deletion virus, even though APC knockdown did seem to affect the overall stability of APC4 and APC5 in pUL21a-independent manner ( Figure S4 ). This suggests that pUL21a-mediated degradation of APC4 and APC5 is independent of APC8.