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

Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9769-74. doi: 10.1073/pnas.96.17.9769.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antigens, Viral
  • H-2 Antigens
  • H-2Kb protein, mouse
  • Nucleoproteins
  • Viral Proteins
  • p40 protein, Borna disease virus