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Journal of Virology, October 2003, p. 11186-11192, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11186-11192.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Borna Disease Virus Nucleoprotein Interacts with the Cdc2-Cyclin B1 Complex

Oliver Planz,1* Stephan Pleschka,2 Katja Oesterle,1 Friederike Berberich-Siebelt,3 Christina Ehrhardt,4,5 Lothar Stitz,1 and Stephan Ludwig4,5

Institut für Immunologie, Bundesforschungsanstalt für Viruskrankheiten der Tiere, Tübingen,1 Institut für Virologie FB 10, Justus-Liebig Universität Giessen, Giessen,2 Institut für Pathologie,3 Institut für Medizinische Strahlenkunde und Zellforschung, Julius-Maximilians Universität Würzburg, Würzburg,5 Institut für Molekulare Medizin, Heinrich-Heine Universität Düsseldorf, Düsseldorf, Germany4

Received 3 March 2003/ Accepted 23 July 2003

Transition from G2 to M phase, a cell cycle checkpoint, is regulated by the Cdc2-cyclin B1 complex. Here, we report that persistent infection with Borna disease virus (BDV), a noncytolytic RNA virus infecting the central nervous system, results in decelerated proliferation of infected host cells due to a delayed G2-to-M transition. Persistent BDV-infected rat fibroblast cells showed reduced proliferation compared to uninfected cells. In pull-down assays we observed an interaction of the viral nucleoprotein with the Cdc2-cyclin B1 complex. Transfection of the viral nucleoprotein but not of the phosphoprotein also results in decelerated proliferation. This phenomenon was found in BDV-susceptible primary rat fibroblast cells and also in primary mouse cells, which are not susceptible to BDV infection. This is the first evidence that the noncytolytic Borna disease virus can manipulate host cell functions via interaction of the viral nucleoprotein with mitotic entry regulators. BDV preferentially infects and persists in nondividing neurons. The present report could give an explanation for this selective choice of host cell by BDV.

* Corresponding author. Mailing address: Institut für Immunologie, Bundesforschungsanstalt für Viruskrankheiten der Tiere, Paul Ehrlich Str. 28, 72076 Tübingen, Germany. Phone: 49 7071 967 254. Fax: 49 7071 967 105. E-mail: oliver.planz{at}tue.bfav.de.

Journal of Virology, October 2003, p. 11186-11192, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11186-11192.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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