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Journal of Virology, December 2001, p. 11700-11708, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11700-11708.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

High-Dose Borna Disease Virus Infection Induces a Nucleoprotein-Specific Cytotoxic T-Lymphocyte Response and Prevention of Immunopathology†

Esther Furrer,1 Thomas Bilzer,2 Lothar Stitz,1 and Oliver Planz1,*

Institut für Immunologie, Bundesforschungsanstalt für Viruskrankheiten der Tiere, Tübingen,1 and Institut für Neuropathologie, Heinrich-Heine-Universität, Düsseldorf,2 Germany

Received 7 May 2001/Accepted 9 August 2001

Experimental Borna disease virus (BDV) infection of rats and natural infection of horses and sheep leads to severe central nervous system disease based on immunopathological pathways. The virus replicates slowly, and the cellular immune response results in immunopathology. CD8+ T cells exert effector cell functions, and their activity results in the destruction of virus-infected cells. Previously, Oldach and colleagues (D. Oldach, M. C. Zink, J. M. Pyper, S. Herzog, R. Rott, O. Narayan, and J. E. Clements, Virology 206:426-434, 1995) have reported protection against Borna disease after inoculation of high-dose cell-adapted BDV. Here we show that the outcome of the infection, i.e., immunopathology versus protection, is simply dependent on the amount of virus used for infection. High-dose BDV (106 FFU) triggers an early virus-specific reaction of the immune system, as demonstrated by strong cellular and humoral responses. In particular, the early presence and function of nucleoprotein-specific CD8+ T cells could be demonstrated in the brain. We present evidence that in a noncytolytic and usually persistent virus infection, high-dose input virus mediates early control of the pathogen due to an efficient induction of an antiviral immune mechanism. From these data, we conclude that immune reactivity, in particular the cytotoxic T-cell response, determines whether the virus is controlled with prevention of the ensuing immunopathological disease or whether a persistent infection is established.

* 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.

dagger Dedicated to Rudolf Rott on the occasion of his 75th birthday.

Journal of Virology, December 2001, p. 11700-11708, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11700-11708.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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