This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.02479-07v1 82/6/3099    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Baur, K. Articles by Staeheli, P. PubMed PubMed Citation Articles by Baur, K. Articles by Staeheli, P.

Antiviral CD8 T Cells Recognize Borna Disease Virus Antigen Transgenically Expressed in either Neurons or Astrocytes

Karen Baur ,^1,, Mathias Rauer,^1, Kirsten Richter,¹ Axel Pagenstecher,³ Jürgen Götz,^2, Jürgen Hausmann,^1* and Peter Staeheli^1*

Department of Virology, University of Freiburg, D-79104 Freiburg, Germany,¹ Division of Psychiatry Research, University of Zürich, CH-8008 Zürich, Switzerland,² Department of Neuropathology, University of Marburg, D-35043 Marburg, Germany³

Received 17 November 2007/ Accepted 24 December 2007

Borna disease virus (BDV) can persistently infect the central nervous system (CNS) of mice. The infection remains nonsymptomatic 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 remains 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 nontransgenic 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 nontransgenic 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.

Published ahead of print on 9 January 2008.

K.B. and M.R. contributed equally to this work.

Present address: Bavarian Nordic GmbH, Fraunhoferstrasse 13, D-82152 Martinsried, Germany.

Present address: Brain and Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia.