As the APC prevents the premature entry of the cell cycle into S phase, we predicted that increased APC activity in the absence of pUL21a would not compromise the ability of HCMV to arrest infected cells at G1/S phase boundary. Consistent with this hypothesis, cells infected with wild type, ADpmUL21a PH-AA , or ADpmUL21a PR-AA virus showed indistinguishable cell cycle profiles throughout infection, with the majority of cells phenotypically arrested in G1 phase ( Figure S6 ). To test if pUL21a was sufficient to alter APC activity, we first analyzed 293T cells that over-expressed pUL21a by transient transfection. Expression of pUL21a alone was sufficient to markedly reduce the levels of APC4 and APC5 ( Figure S7A) , and as expected, geminin and Cdh1 levels were elevated in these cells. These pUL21a-expressing cells were largely arrested in G2/ M phase ( Figure S7B ), failed to multiply, and ultimately died ( Figure S7C ). The biological characteristics of pUL21a-expressing cells are therefore consistent with reduced APC activity.