Previous studies of Epstein-Barr virus (EBV) replication focused mainly on the 
viral and cellular factors involved in replication compartment assembly and 
controlling the cell cycle. However, little is known about how EBV reorganizes 
nuclear architecture and the chromatin territories. In EBV-positive 
nasopharyngeal carcinoma NA cells or Akata cells, we noticed that cellular 
chromatin becomes highly condensed upon EBV reactivation. In searching for the 
possible mechanisms involved, we found that transient expression of EBV BGLF4 
kinase induces unscheduled chromosome condensation, nuclear lamina disassembly, 
and stress fiber rearrangements, independently of cellular DNA replication and 
Cdc2 activity. BGLF4 interacts with condensin complexes, the major components in 
mitotic chromosome assembly, and induces condensin phosphorylation at Cdc2 
consensus motifs. BGLF4 also stimulates the decatenation activity of 
topoisomerase II, suggesting that it may induce chromosome condensation through 
condensin and topoisomerase II activation. The ability to induce chromosome 
condensation is conserved in another gammaherpesvirus kinase, murine herpesvirus 
68 ORF36. Together, these findings suggest a novel mechanism by which 
gammaherpesvirus kinases may induce multiple premature mitotic events to provide 
more extrachromosomal space for viral DNA replication and successful egress of 
nucleocapsid from the nucleus.