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Journal of Virology, May 2001, p. 4871-4877, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4871-4877.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

MEK-Specific Inhibitor U0126 Blocks Spread of Borna Disease Virus in Cultured Cells

Oliver Planz,1,* Stephan Pleschka,2 and Stephan Ludwig3

Institut für Immunologie, Bundesforschungsanstalt für Viruskrankheiten der Tiere, Tübingen,1 Institut für Virologie, Fachbereich Veterinär-Medizin, Justus-Liebig Universität, Giessen,2 and Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), Würzburg,3 Germany

Received 17 October 2000/Accepted 21 February 2001

Borna disease virus (BDV) is a highly neurotropic virus that causes Borna disease, a virus-induced immune-mediated encephalomyelitis, in a variety of warm-blooded animals. Recent studies reported that BDV can be detected in patients with psychiatric disorders. BDV is noncytopathic, replicates in the nucleus of infected cells, and spreads intraaxonally in vivo. Upon infection of susceptible cultured cells, virus can be detected in foci. Little is known about the cellular components required for BDV replication. Here, we show that the cellular Raf/MEK/ERK signaling cascade is activated upon infection with BDV. In the presence of the MEK-specific inhibitor U0126, cells get infected with BDV; however, there is a block in virus spread to neighboring cells. The effect of the inhibitor on virus spread was still observed when the compound was added 2 h postinfection but not if treatment was initiated as late as 4 h after infection. Our results provide new insights into the BDV-host cell interaction and show that virus infection can be controlled with drugs interfering with a cellular signaling pathway. Since concentrations of the MEK inhibitor required to block BDV focus formation are not toxic for the host cells, our finding may be important with respect to antiviral drug development.

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

Journal of Virology, May 2001, p. 4871-4877, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4871-4877.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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