In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 17 ( 1999-08-17), p. 9769-9774
Abstract:
Infection of neonates with Borna disease virus (BDV) induces severe meningoencephalitis and neurological disorder in wild-type but not in β 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.96.17.9769
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1999
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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