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Journal of Virology, April 2003, p. 4283-4290, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.4283-4290.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Selective Virus Resistance Conferred by Expression of Borna Disease Virus Nucleocapsid Components

Till Geib, Christian Sauder, Sascha Venturelli, Christel Hässler, Peter Staeheli,* and Martin Schwemmle*

Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany

Received 19 July 2002/ Accepted 27 December 2002

Persistent viral infections can render host cells resistant to superinfection with closely related viruses by largely uncharacterized mechanisms. We present evidence for superinfection exclusion in brains of Borna disease virus (BDV)-infected rats and in persistently infected Vero cells, and we suggest that acquired resistance to BDV is due to unbalanced intracellular levels of viral nucleocapsid components. We observed that expression of BDV protein P, N, or X rendered human cells resistant to subsequent challenge with BDV but not with other RNA viruses, indicating that incorrect stoichiometry of nucleocapsid components selectively blocked the polymerase activity of incoming viruses. Vero cells containing high levels of an untranslatable BDV-N transcript remained virus susceptible, demonstrating that viral protein rather than RNA mediated resistance. Transient overexpression of BDV-P in persistently infected Vero cells was also remarkably effective against BDV, indicating that the intracellular balance of viral nucleocapsid components could serve as a target for future therapeutic antiviral strategies.

* Corresponding author. Mailing address: Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany. Phone: 49-761-203-6579. Fax: 49-761-203-5053. E-mail: staeheli{at}ukl.uni-freiburg.de.

* Corresponding author. Present address: Institute of Medical Virology, University of Zürich, Gloriastrasse 30, CH-8028 Zürich, Switzerland. Phone: 41-1-634-4906. Fax: 41-1-634-2789. E-mail: mschwemm{at}immv.unizh.ch.

Journal of Virology, April 2003, p. 4283-4290, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.4283-4290.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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