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T cell ignorance in mice to Borna disease virus can be overcome by peripheral expression of the viral nucleoprotein

Academic Article
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Overview

authors

  • Hausmann, J.
  • Hallensleben, W.
  • de la Torre, Juan
  • Pagenstecher, A.
  • Zimmermann, C.
  • Pircher, H.
  • Staheli, P.

publication date

  • August 1999

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Infection of neonates with Borna disease virus (BDV) induces severe meningoencephalitis and neurological disorder in wild-type but not in beta(2)-microglobulin-deficient mice of strain MRL (H-2(k)). Temporary in vivo depletion of CD8(+) T cells delayed BDV-induced disease for several weeks. Depletion of CD4(+) T cells had a similar beneficial effect, indicating that the BDV-induced neurological disorder in mice is a CD4(+) T cell-dependent immunopathological process that is mediated by CD8(+) T cells. Lymphocytes prepared from brains of diseased mice were mainly from the CD8(+) T cell subset. They showed up-regulation of activation markers and exerted strong MHC I-restricted cytotoxic activity against target cells expressing the BDV nucleoprotein p40. Infection of B10.BR (H-2(k)) or congenic C57BL/10 (H-2(b)) mice resulted in symptomless, lifelong persistence of BDV in the brain. Superinfection with a recombinant vaccinia virus expressing BDV p40 but not with other vaccinia viruses induced severe neurological disease and encephalitis in persistently infected B10.BR mice but not in persistently infected C57BL/10 mice, indicating that the disease-inducing T cell response is restricted to the nucleoprotein of BDV in H-2(k) mice. Our results demonstrate that the cellular arm of the immune system may ignore the presence of a replicating virus in the central nervous system until proper antigenic stimulation at a peripheral site triggers the antiviral response.

subject areas

  • Animals
  • Antigens, Viral
  • Borna Disease
  • Borna disease virus
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • H-2 Antigens
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Nucleoproteins
  • T-Lymphocytes
  • Up-Regulation
  • Viral Proteins
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Identity

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.96.17.9769

PubMed ID

  • 10449769
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Additional Document Info

start page

  • 9769

end page

  • 9774

volume

  • 96

issue

  • 17

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