Immune-mediated pathogenesis of Borna disease.
Abstract: Borna disease is an endemic progressive encephalomyelitis of horses and sheep prevalent in central Europe. A wide variety of animal species, ranging from chickens to primates can be infected experimentally with the causative virus, which is only poorly characterized. Furthermore, BD virus-specific antibodies have been detected in sera and cerebrospinal fluids of psychiatric patients. Our studies on the pathogenesis of BD have shown that-at least in rats-the disease is not caused by the infecting virus itself, but by a virus-induced immunopathological reaction. Thus, after intracerebral infection immunoincompetent rats do not get the disease despite persistent virus replication in cells of the central nervous system. However, after adoptive transfer of immune cells from diseased rats, immunoincompetent rats exhibit full-blown BD. Recently, we have been successful in establishing a virus-specific T cell line of the helper/inducer phenotype (CD4+). This T cell was shown to play an important role in the pathogenesis of BD, suggesting that the disease is caused by a delayed type hypersensitivity reaction.
Publication Date: 1988-11-01 PubMed ID: 3265562DOI: 10.1016/s0176-6724(88)80166-4Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates Borna disease, an endemic disease affecting horses and sheep in Central Europe, and suggests that it is not directly caused by the virus but rather by an immune response it triggers. The disease’s potential connection to psychiatric patients was also explored.
Introduction and Background
- The paper revolves around Borna disease, a progressive encephalomyelitis (inflammation of the brain and spinal cord) prevalent in Central Europe that affects horses and sheep.
- Research indicates that this disease can affect a variety of species through experimental infection, from chickens to primates, and is caused by a virus that is not well understood.
- A significant finding underpins this research: Borna Disease virus-specific antibodies have been recognised in sera and cerebrospinal fluids of psychiatric patients, suggesting a possible connection between the disease and psychiatric conditions.
Findings on Borna Disease Pathogenesis
- Through their studies, researchers have discovered that the pathogenesis of Borna Disease – in rats at least – is not caused directly by the infecting virus. Instead, it’s caused by an immunopathological reaction that the virus induces.
- Immunocompromised rats infected intracerebrally with the virus do not develop the disease, even though the virus replicates persistently in cells of their central nervous system. This supports the idea that the disease is not directly caused by the virus.
- However, when immune cells from rats with Borna Disease are transferred to these immunocompromised rats, the recipients show full symptoms of the disease. This suggests that the disease emerges in response to immune activity rather than from viral activity directly.
Role of T Cells in the Disease
- Researchers were successful in establishing a virus-specific T cell line with a helper/inducer phenotype (CD4+), believed to play a critical role in the disease’s pathogenesis.
- The findings suggest that Borna Disease may result from a delayed type hypersensitivity reaction, a specific kind of immune response usually caused by an antigen, rather than direct viral damage.
- This particular type of T cell (CD4+) can contribute to this immune response, reinforcing the understanding that this disease is rooted in immune reactions and not in the direct effects of the virus.
Cite This Article
APA
Rott R, Herzog S, Richt J, Stitz L.
(1988).
Immune-mediated pathogenesis of Borna disease.
Zentralbl Bakteriol Mikrobiol Hyg A, 270(1-2), 295-301.
https://doi.org/10.1016/s0176-6724(88)80166-4 Publication
Researcher Affiliations
- Institut für Virologie, Justus-Liebig-Universität Giessen.
MeSH Terms
- Animals
- Animals, Newborn
- Borna Disease / etiology
- Borna Disease / immunology
- Hypersensitivity, Delayed
- Immune Tolerance
- Rats
- Rats, Inbred Lew
Citations
This article has been cited 13 times.- Petzold J, Gartner AM, Malberg S, Link JB, Bücking B, Lierz M, Herden C. Tissue Distribution of Parrot Bornavirus 4 (PaBV-4) in Experimentally Infected Young and Adult Cockatiels (Nymphicus hollandicus).. Viruses 2022 Oct 1;14(10).
- Rauch J, Steffen JF, Muntau B, Gisbrecht J, Pörtner K, Herden C, Niller HH, Bauswein M, Rubbenstroth D, Mehlhoop U, Allartz P, Tappe D. Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease.. Emerg Microbes Infect 2022 Dec;11(1):1843-1856.
- Kim TJ, Cha KS, Lee S, Yang TW, Kim KT, Park BS, Jun JS, Lim JA, Byun JI, Sunwoo JS, Shin JW, Kim KH, Lee SK, Jung KY. Brain regions associated with periodic leg movements during sleep in restless legs syndrome.. Sci Rep 2020 Jan 31;10(1):1615.
- Tappe D, Schmidt-Chanasit J, Rauch J, Allartz P, Herden C. Immunopathology of Fatal Human Variegated Squirrel Bornavirus 1 Encephalitis, Germany, 2011-2013.. Emerg Infect Dis 2019 Jun;25(6):1058-1065.
- Tappe D, Schlottau K, Cadar D, Hoffmann B, Balke L, Bewig B, Hoffmann D, Eisermann P, Fickenscher H, Krumbholz A, Laufs H, Huhndorf M, Rosenthal M, Schulz-Schaeffer W, Ismer G, Hotop SK, Brönstrup M, Ott A, Schmidt-Chanasit J, Beer M. Occupation-Associated Fatal Limbic Encephalitis Caused by Variegated Squirrel Bornavirus 1, Germany, 2013.. Emerg Infect Dis 2018 Jun;24(6):978-987.
- Guo J, Shivaprasad HL, Rech RR, Heatley JJ, Tizard I, Payne S. Characterization of a new genotype of avian bornavirus from wild ducks.. Virol J 2014 Nov 19;11:197.
- Gancz AY, Kistler AL, Greninger AL, Farnoushi Y, Mechani S, Perl S, Berkowitz A, Perez N, Clubb S, DeRisi JL, Ganem D, Lublin A. Experimental induction of proventricular dilatation disease in cockatiels (Nymphicus hollandicus) inoculated with brain homogenates containing avian bornavirus 4.. Virol J 2009 Jul 9;6:100.
- Stitz L, Nöske K, Planz O, Furrer E, Lipkin WI, Bilzer T. A functional role for neutralizing antibodies in Borna disease: influence on virus tropism outside the central nervous system.. J Virol 1998 Nov;72(11):8884-92.
- Rubin SA, Waltrip RW 2nd, Bautista JR, Carbone KM. Borna disease virus in mice: host-specific differences in disease expression.. J Virol 1993 Jan;67(1):548-52.
- Deschl U, Stitz L, Herzog S, Frese K, Rott R. Determination of immune cells and expression of major histocompatibility complex class II antigen in encephalitic lesions of experimental Borna disease.. Acta Neuropathol 1990;81(1):41-50.
- Trautwein G. Immune mechanisms in the pathogenesis of viral diseases: a review.. Vet Microbiol 1992 Nov;33(1-4):19-34.
- Stitz L, Sobbe M, Bilzer T. Preventive effects of early anti-CD4 or anti-CD8 treatment on Borna disease in rats.. J Virol 1992 Jun;66(6):3316-23.
- Richt JA, Stitz L. Borna disease virus-infected astrocytes function in vitro as antigen-presenting and target cells for virus-specific CD4-bearing lymphocytes.. Arch Virol 1992;124(1-2):95-109.
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