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Journal of Virology, April 2004, p. 3621-3632, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3621-3632.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Transgenic Mice Expressing the Nucleoprotein of Borna Disease Virus in either Neurons or Astrocytes: Decreased Susceptibility to Homotypic Infection and Disease

Mathias Rauer,1 Jürgen Götz,2 Daniel Schuppli,2 Peter Staeheli,1 and Jürgen Hausmann1*

Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, D-79104 Freiburg, Germany,1 Division of Psychiatry Research, University of Zürich, CH-8008 Zürich, Switzerland2

Received 6 August 2003/ Accepted 15 December 2003

The nucleoprotein (N) of Borna disease virus (BDV) is the major target of the disease-inducing antiviral CD8 T-cell response in the central nervous system of mice. We established two transgenic mouse lines which express BDV-N in either neurons (Neuro-N) or astrocytes (Astro-N). Despite strong transgene expression, neurological disease or gross behavioral abnormalities were not observed in these animals. When Neuro-N mice were infected as adults, replication of BDV was severely impaired and was restricted to brain areas with a low density of transgene-expressing cells. Notably, the virus failed to replicate in the transgene-expressing granular and pyramidal neurons of the hippocampus (which are usually the preferred host cells of BDV). When Neuro-N mice were infected within the first 5 days of life, replication of BDV was not suppressed in most neurons, presumably because the onset of transgene expression in the brain occurred after these cells became infected with BDV. Astro-N mice remained susceptible to BDV infection, but they were resistant to BDV-induced neurological disorder. Unlike their nontransgenic littermates, Neuro-N mice with persistent BDV infection did not develop neurological disease after immunization with a vaccinia virus vector expressing BDV-N. In contrast to the situation in wild-type mice, this treatment also failed to induce N-specific CD8 T cells in the spleens of both transgenic mouse lines. Thus, while resistance to BDV infection in N-expressing neurons appeared to result from untimely expression of a viral nucleocapsid component, the resistance to BDV-induced neuropathology probably resulted from immunological tolerance.

* Corresponding author. Mailing address: Department of Virology, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany. Phone: 49-761-203-6622. Fax: 49-761-203-5350. E-mail: hausmann{at}ukl.uni-freiburg.de.

Journal of Virology, April 2004, p. 3621-3632, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3621-3632.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Richter, K., Hausmann, J., Staeheli, P. (2009). Interferon-{gamma} Prevents Death of Bystander Neurons during CD8 T Cell Responses in the Brain. Am. J. Pathol. 174: 1799-1807 [Abstract] [Full Text]  
  • Baur, K., Rauer, M., Richter, K., Pagenstecher, A., Gotz, J., Hausmann, J., Staeheli, P. (2008). Antiviral CD8 T Cells Recognize Borna Disease Virus Antigen Transgenically Expressed in either Neurons or Astrocytes. J. Virol. 82: 3099-3108 [Abstract] [Full Text]  
  • Ackermann, A., Kugel, D., Schneider, U., Staeheli, P. (2007). Enhanced polymerase activity confers replication competence of Borna disease virus in mice. J. Gen. Virol. 88: 3130-3132 [Abstract] [Full Text]  
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