Human cytomegalovirus infection inhibits G(1)/S transition

Cell cycle progression during cytomegalovirus infection was investigated by fluorescence-activated cell sorter (FACS) analysis of the DNA content in growth-arrested as well as serum-stimulated human fibroblasts. Virus-infected cells maintained in either low (0.2%) or high (10%) serum failed to progress into S phase and failed to divide. DNA content analysis in the presence of G(1)/S (hydroxyurea and mimosine) and G(2)/M (nocodazole and colcemid) inhibitors demonstrated that upon virus infection of quiescent (G(0)) cells, the cell cycle did not progress beyond the G(1)/S border even after serum stimulation. Proteins which normally indicate G(1)/S transition (proliferating cell nuclear antigen [PCNA]) or G(2)/M transition (cyclin B-1) were elevated by virus infection. PCNA levels were induced in infected cells and exhibited a punctate pattern of nuclear staining instead of the diffuse pattern observed in mock-infected cells. Cyclin B-1 was induced in infected cells which exhibited a G(1)/S DNA content by FACS analysis, suggesting that expression of this keg cell cycle function was dramatically altered by viral functions. These data demonstrate that contrary to expectations, cytomegalovirus inhibits normal cell cycle progression. The host cell is blocked prior to S phase to provide a favorable environment for viral replication.