The S phase of the cell cycle and its perturbation by human cytomegalovirus

Abstract

Human cytomegalovirus (HCMV) is a complex human herpesvirus that is known to productively infect a wide range of cell types. In addition, it has been suggested to contribute to some proliferative disorders, particularly atherosclerosis. Consistent with this, a number of studies have shown that HCMV profoundly affects normal cell cycle control. Specifically, the virus can stimulate early entry into S phase thus ensuring adequate resources for viral DNA replication. Importantly, however, the virus concomitantly inhibits potentially competing cellular DNA synthesis allowing cellular precursors to be used for viral but not cellular DNA replication. The mechanisms by which HCMV perturbs S phase entry involve interactions between the virus and the cellular replication machinery such that formation of competent pre-replication complexes (Pre-RC) at cellular origins of replication is restricted in infected cells.