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Journal of Virology, September 2005, p. 11716-11723, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11716-11723.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Borna Disease Virus Replication in Organotypic Hippocampal Slice Cultures from Rats Results in Selective Damage of Dentate Granule Cells

Daniel Mayer,1 Heike Fischer,2 Urs Schneider,1 Bernd Heimrich,2* and Martin Schwemmle1*

Department of Virology, Institute for Medical Microbiology and Hygiene,1 Institute of Anatomy and Cell Biology, University of Freiburg, D-79104 Freiburg, Germany2

Received 24 March 2005/ Accepted 15 June 2005

In the hippocampus of Borna disease virus (BDV)-infected newborn rats, dentate granule cells undergo progressive cell death. BDV is noncytolytic, and the pathogenesis of this neurodevelopmental damage in the absence of immunopathology remains unclear. A suitable model system to study early events of the pathology is lacking. We show here that organotypic hippocampal slice cultures from newborn rat pups are a suitable ex vivo model to examine BDV neuropathogenesis. After challenging hippocampal slice cultures with BDV, we observed a progressive loss of calbindin-positive granule cells 21 to 28 days postinfection. This loss was accompanied by reduced numbers of mossy fiber boutons when compared to mock-infected cultures. Similarly, the density of dentate granule cell axons, the mossy fiber axons, appeared to be substantially reduced. In contrast, hilar mossy cells and pyramidal neurons survived, although BDV was detectable in these cells. Despite infection of dentate granule cells 2 weeks postinfection, the axonal projections of these cells and the synaptic connectivity patterns were comparable to those in mock-infected cultures, suggesting that BDV-induced damage of granule cells is a postmaturation event that starts after mossy fiber synapses are formed. In summary, we find that BDV infection of rat organotypic hippocampal slice cultures results in selective neuronal damage similar to that observed with infected newborn rats and is therefore a suitable model to study BDV-induced pathology in the hippocampus.


* Corresponding author. Mailing address for Martin Schwemmle: Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany. Phone: 49-761-203-6526. Fax: 49-761-203-6639. E-mail: martin.schwemmle{at}uniklinik-freiburg.de. Mailing address for Bernd Heimrich: Institute of Anatomy, University of Freiburg, Albertstr. 23, D-79104 Freiburg, Germany. Phone: 49-761-203-8418. Fax: 49-761-203-8417. E-mail: bernd.heimrich{at}zfn.uni-freiburg.de.


Journal of Virology, September 2005, p. 11716-11723, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11716-11723.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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