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J Virol, May 1998, p. 4379-4386, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Borna Disease Virus-Induced Neurological Disorder in Mice: Infection of Neonates Results in Immunopathology

Wiebke Hallensleben,1 Martin Schwemmle,1 Jürgen Hausmann,1 Lothar Stitz,2 Benedikt Volk,3 Axel Pagenstecher,3 and Peter Staeheli1,*

Abteilung Virologie, Institut für Medizinische Mikrobiologie & Hygiene, Universität Freiburg, 79008 Freiburg,1 Institut für Neuropathologie, Universität Freiburg, 79106 Freiburg,3 and Institut für Impfstoffe, Bundesforschungsanstalt für Viruskrankheiten der Tiere, 72076 Tübingen,2 Germany

Received 17 December 1997/Accepted 2 February 1998

Borna disease virus (BDV) is a neurotropic nonsegmented negative-stranded RNA virus that persistently infects warm-blooded animals. In horses and other natural animal hosts, infections with BDV cause meningoencephalitis and behavioral disturbances. Experimental infection of adult mice takes a nonsymptomatic course, an observation previously believed to indicate that this animal species is not suitable for pathogenesis studies. We now demonstrate that BDV frequently induces severe neurological disease in infected newborn mice. Signs of neurological disease were first observed 4 to 6 weeks after intracerebral infection. They included a characteristic nonphysiological position of the hind limbs at an early stage of the disease and paraparesis at a later stage. Histological examination revealed large numbers of perivascular and meningeal inflammatory cells in brains of diseased mice and, unexpectedly, no increase in immunoreactivity to glial fibrillar acidic protein. The incidence and severity of BDV-induced disease varied dramatically among mouse strains. While only 13% of the infected C57BL/6 mice showed disease symptoms, which were mostly transient, more than 80% of the infected MRL mice developed severe neurological disorder. In spite of these differences in susceptibility to disease, BDV replicated to comparable levels in the brains of mice of the various strains used. Intracerebral infections of newborn beta 2-microglobulin-deficient C57BL/6 and MRL mice, which both lack CD8+ T cells, did not result in meningoencephalitis or neurological disease, indicating that the BDV-induced neurological disorder in mice is a cytotoxic T-cell-mediated immunopathological process. With this new animal model it should now be possible to characterize the disease-inducing immune response to BDV in more detail.

* Corresponding author. Mailing address: Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, D-79008 Freiburg, Germany. Phone: 49-761-203-6579. Fax: 49-761-203-6562. E-mail: staeheli{at}ukl.uni-freiburg.de.

J Virol, May 1998, p. 4379-4386, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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