JVI Accepts, published online ahead of print on 9 January 2008

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J. Virol. doi:10.1128/JVI.02479-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Antiviral CD8 T cells recognize Borna disease virus antigen transgenically expressed in either neurons or astrocytes

Karen Baur, Mathias Rauer, Kirsten Richter, Axel Pagenstecher, Jürgen Götz, Jürgen Hausmann^*, and Peter Staeheli^*

Department of Virology, University of Freiburg, D-79104 Freiburg, Germany; Division of Psychiatry Research, University of Zürich, CH-8008 Zürich, Switzerland; Department of Neuropathology, University of Marburg, D-35043 Marburg, Germany

^* To whom correspondence should be addressed. Email: juergen.hausmann{at}bavarian-nordic.com. peter.staeheli{at}uniklinik-freiburg.de.

Borna disease virus (BDV) can persistently infect the central nervous system of mice. The infection remains non-symptomatic as long as antiviral CD8 T cells do not infiltrate the infected brain. BDV mainly infects neurons which reportedly carry few if any major histocompatibility complex class I molecules on the surface. Therefore, it remained unclear whether T cells can recognize replicating virus in these cells or whether cross-presentation of viral antigen by other cell types is important for immune recognition of BDV. To distinguish between these possibilities we used two lines of transgenic mice that strongly express the N protein of BDV in either neurons (Neuro-N) or astrocytes (Astro-N). Since these animals are tolerant to the neo-self antigen, we adoptively transferred T cells with specificity for BDV-N. In non-transgenic mice persistently infected with BDV, the transferred cells accumulated in the brain parenchyma along with immune cells of host origin and efficiently induced neurological disease. Neurological disease was also observed if antiviral T cells were injected into the brains of Astro-N or Neuro-N, but not non-transgenic control mice. Our results demonstrate that CD8 T cells can recognize foreign antigen on neurons and astrocytes even in the absence of infection or inflammation, indicating that these CNS cell types are playing an active role in immune recognition of viruses.

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• 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]