Human cytomegalovirus 86-kilodalton IE2 protein blocks cell cycle progression in G1

The 86-kDa IE2 protein of human cytomegalovirus (HCMV) is an important regulator of viral and host cell gene expression. Still, besides its function as a transcription factor, little is known about the biological activities of IE2. Here, we show that IE2 can induce a G(1) arrest in several different cell lines, including HCMV-permissive U-373 cells. The known transcriptional activation domains of IE2 are dispensable for G(1) arrest, favoring a posttranscriptional mechanism mediating this cell cycle effect. We show that like human primary fibroblasts U-373 cells arrest in G(1) upon infection with HCMV. This G(1) arrest occurs within 24 h after infection and in proliferating cells depends on viral gene expression. Our data therefore suggest that IE2 is at least partially responsible for blocking the transition from G(1) to S phase, which is induced when cells are infected with HCMV.