title: T cell ignorance in mice to Borna disease virus can be overcome by peripheral expression of the viral nucleoprotein.
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.
authors.affiliation: Department of Virology, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hausmann
authors.forename: W
authors.initials: W
authors.lastname: Hallensleben
authors.forename: J C
authors.initials: JC
authors.lastname: de la Torre
authors.forename: A
authors.initials: A
authors.lastname: Pagenstecher
authors.forename: C
authors.initials: C
authors.lastname: Zimmermann
authors.forename: H
authors.initials: H
authors.lastname: Pircher
authors.forename: P
authors.initials: P
authors.lastname: Staeheli
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001890:Borna Disease / Q000276:immunology*; D001891:Borna disease virus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009698:Nucleoproteins / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation; D014764:Viral Proteins / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D009698:Nucleoproteins; D014764:Viral Proteins; C077347:p40 protein, Borna disease virus