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Journal of Virology, May 2007, p. 5166-5180, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.00120-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus BGLF4 Kinase Induces Premature Chromosome Condensation through Activation of Condensin and Topoisomerase II{triangledown} ,{dagger}

Chung-Pei Lee,1 Jen-Yang Chen,1,2 Jiin-Tarng Wang,1 Keiji Kimura,3 Ai Takemoto,3 Chih-Chung Lu,1 and Mei-Ru Chen1*

Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan,1 National Health Research Institutes, Taipei, Taiwan,2 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Japan3

Received 18 January 2007/ Accepted 5 March 2007

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.

* Corresponding author. Mailing address: No. 1, 1st Sec. Jen-Ai Road, Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. Phone: 886-2-23123456, ext. 8298. Fax: 886-2-23915293. E-mail: mrc{at}ntu.edu.tw

{triangledown} Published ahead of print on 14 March 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, May 2007, p. 5166-5180, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.00120-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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