Transgenic mice expressing Borna disease virus nucleoprotein in the CNS.

The Borna disease virus (BDV) nucleoprotein (N) has been previously shown to be the main target of the disease-inducing antiviral CD8 T cell response. Thus, its expression pattern and cell surface presentation in cells of the CNS are major determinants for the development of BDV-induced immunopathology. In mice as well as in rats and natural hosts like horses and sheep, the virus is mainly found in neurons and also in astrocytes, which provide mechanical and metabolic support to neurons. In this project, we want to establish various lines of transgenic mice expressing the Borna disease virus nucleoprotein in neurons and astrocytes either exclusively or in combination to answer two major questions: First, we want to dissect factors that are minimally required for initiation and enhancement of inflammation in the CNS and second, we want to clarify on which CNS cell type the CD8 T cells do actually recognize the nucleoprotein expression and thus BDV infection. Candidate factors to promote inflammation that may be required additional to recognition of infected cells via MHC I-T cell receptor interaction might be interferons, chemokines or other as yet unidentified molecules. A second aspect of the N-transgenic mouse model might be its role as an in vivo test system for the observed resistance of BDV-infected cells to superinfection due to pre-existing expression of one or more viral gene products. N is one candidate viral protein that might mediate this effect. In case of a role for N in this phenomenon, this aspect will be investigated in collaboration with the group of Dr. Martin Schwemmle in our institute (see project "Mechanisms of cellular resistance of Borna disease virus-infected cells to superinfection").

Additional information: http://www.ukl.uni-freiburg.de/microbio
contact person: Prof. Dr. Peter Staeheli
Phone: (0761) 203.6622
Email: peter.staeheli@uniklinik-freiburg.de

Start of project: 01.01.2000
End of project: 31.03.2005

Albert-Ludwigs-University Freiburg
Hausmann Jürgen, Stäheli Peter
Department für Medizinische Mikrobiologie und Hygiene
Institut für Virologie
Hermann-Herder-Strasse 11
79104 Freiburg
Germany

Phone: +49 761 203 6534
Fax: +49 761 203 6626
http://www.virologie.uniklinik-freiburg.de
Actual Research Report

• Deutsche Forschungsgemeinschaft, DFG

Transgenic mice, Borna disease virus