Human cytomegalovirus 86-kilodalton IE2 protein blocks cell cycle progression in G(1).
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.
Wiebusch
L
L
Laboratory for Molecular Biology, Department of Pediatrics, Charité, Humboldt-University, D-10098 Berlin, Germany.
Hagemeier
C
C
D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology*; D005434:Flow Cytometry; D016193:G1 Phase; D015967:Gene Expression Regulation, Viral; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D015151:Immunoblotting; D008562:Membrane Glycoproteins; D010957:Plasmids / Q000235:genetics; D016196:S Phase; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins; D014764:Viral Proteins
C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D015534:Trans-Activators; C077406:UL115 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus