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Journal of Virology, November 2001, p. 10460-10466, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10460-10466.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

CD8+ T Lymphocytes Mediate Borna Disease Virus-Induced Immunopathology Independently of Perforin

Jürgen Hausmann,* Karin Schamel, and Peter Staeheli

Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79104 Freiburg, Germany

Received June 4 2001/Accepted 8 August 2001

Perforin-mediated lysis of target cells is the major antiviral effector mechanism of CD8+ T lymphocytes. We have analyzed the role of perforin in a mouse model for CD8+ T-cell-mediated central nervous system (CNS) immunopathology induced by Borna disease virus. When a defective perforin gene was introduced into the genetic background of the Borna disease-susceptible mouse strain MRL, the resulting perforin-deficient mice developed strong neurological disease in response to infection indistinguishable from that of their perforin-expressing littermates. The onset of disease was slightly delayed. Brains of diseased perforin-deficient mice showed similar amounts and a similar distribution of CD8+ T cells as wild-type animals. Perforin deficiency had no impact on the kinetics of viral spread through the CNS. Unlike brain lymphocytes from diseased wild-type mice, lymphocytes from perforin-deficient MRL mice showed no in vitro cytolytic activity towards target cells expressing the nucleoprotein of Borna disease virus. Taken together, these results demonstrate that CD8+ T cells mediate Borna disease independent of perforin. They further suggest that the pathogenic potential of CNS-infiltrating CD8+ T cells does not primarily reside in their lytic activity but rather in other functions.


* Corresponding author. Mailing address: Department of Virology, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany. Phone: 49-761-203-6622. Fax: 49-761-203-6562. E-mail: hausmann{at}ukl.uni-freiburg.de.


Journal of Virology, November 2001, p. 10460-10466, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10460-10466.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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