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Journal of Virology, October 2007, p. 11187-11194, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.00742-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pathogenic Potential of Borna Disease Virus Lacking the Immunodominant CD8 T-Cell Epitope{triangledown}

Kirsten Richter, Karen Baur,§ Andreas Ackermann, Urs Schneider, Jürgen Hausmann,§ and Peter Staeheli*

Department of Virology, University of Freiburg, D-79104 Freiburg, Germany

Received 5 April 2007/ Accepted 26 July 2007

Borna disease virus (BDV) is a highly neurotropic, noncytolytic virus. Experimentally infected B10.BR mice remain healthy unless specific antiviral T cells that infiltrate the infected brain are triggered by immunization. In contrast, infected MRL mice spontaneously mount an antiviral T-cell response that can result in meningoencephalitis and neurological disease. The antiviral T cells may, alternatively, eliminate the virus without inducing disease if they are present in sufficient numbers before the virus replicates to high titers. Since the immune response of H-2k mice is directed mainly against the epitope TELEISSI located in the viral nucleoprotein N, we generated BDV mutants that feature TQLEISSI in place of TELEISSI. We show that adoptive transfer of BDV N-specific CD8 T cells induced neurological disease in B10.BR mice persistently infected with wild-type BDV but not with the mutant virus expressing TQLEISSI. Surprisingly, the mutant virus replicated less well in adult MRL wild-type mice than in mutant mice lacking mature CD8 T cells. Furthermore, when MRL mice were infected with the TQLEISSI-expressing BDV mutant as newborns, neurological disease was observed, although at a lower rate and with slower kinetics than in mice infected with wild-type virus. These results confirm that TELEISSI is the major CD8 T-cell epitope in H-2k mice and suggest that unidentified minor epitopes are present in the BDV proteome which are recognized rather efficiently by antiviral T cells if the dominant epitope is absent.

* Corresponding author. Mailing address: Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany. Phone: 49-761-203-6579. Fax: 49-761-203-5350. E-mail: peter.staeheli{at}uniklinik-freiburg.de

{triangledown} Published ahead of print on 8 August 2007.

§ Present address: Bavarian Nordic GmbH, Fraunhoferstrasse 13, D-82152 Martinsried, Germany.

Journal of Virology, October 2007, p. 11187-11194, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.00742-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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