High-dose Borna disease virus infection induces a nucleoprotein-specific cytotoxic T-lymphocyte response and prevention of immunopathology.
Abstract: Experimental Borna disease virus (BDV) infection of rats and natural infection of horses and sheep leads to severe central nervous system disease based on immunopathological pathways. The virus replicates slowly, and the cellular immune response results in immunopathology. CD8(+) T cells exert effector cell functions, and their activity results in the destruction of virus-infected cells. Previously, Oldach and colleagues (D. Oldach, M. C. Zink, J. M. Pyper, S. Herzog, R. Rott, O. Narayan, and J. E. Clements, Virology 206:426-434, 1995) have reported protection against Borna disease after inoculation of high-dose cell-adapted BDV. Here we show that the outcome of the infection, i.e., immunopathology versus protection, is simply dependent on the amount of virus used for infection. High-dose BDV (10(6) FFU) triggers an early virus-specific reaction of the immune system, as demonstrated by strong cellular and humoral responses. In particular, the early presence and function of nucleoprotein-specific CD8(+) T cells could be demonstrated in the brain. We present evidence that in a noncytolytic and usually persistent virus infection, high-dose input virus mediates early control of the pathogen due to an efficient induction of an antiviral immune mechanism. From these data, we conclude that immune reactivity, in particular the cytotoxic T-cell response, determines whether the virus is controlled with prevention of the ensuing immunopathological disease or whether a persistent infection is established.
Publication Date: 2001-11-02 PubMed ID: 11689651PubMed Central: PMC114756DOI: 10.1128/JVI.75.23.11700-11708.2001Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study discusses how high-dose Borna Disease Virus (BDV) infection triggers an early specific immune system reaction that controls this normally persistent and noncytolytic virus, potentially preventing immune system disorder. This early reaction is primarily driven by the presence and function of nucleoprotein-specific CD8(+) T cells.
Research Purpose and Context
- The study seeks to understand the impact of the level of virus used in infection on the immune response and the pathogenesis of Borna Disease Virus (BDV). BDV is a slow replicating virus that can cause severe central nervous system disease in animals like rats, horses, and sheep through immune reaction pathways.
- Earlier research by Oldach and colleagues posited that high doses of BDV could protect against the disease.
Research Methodology and Findings
- The researchers infected subjects with high-dose BDV (106 FFU) and observed that it invokes an immediate, strong cellular and humoral response.
- The response was identified in the early presence and functionality of nucleoprotein-specific CD8(+) T cells in the brain, known to destroy virus-infected cells and manage the core of the immune response.
- The researchers thus demonstrated that a high-dose input virus could control the typically persistent and noncytolytic BDV through the efficient initiation of an antiviral immune reaction.
Implications and Conclusions
- The study concludes that the immune reactivity plays a significant role in determining whether the virus is effectively controlled and subsequent immune disorder is prevented or whether a persistent infection is established.
- Essentially, the outcome of the infection – whether it leads to immunopathology or protection – is heavily dependent on the amount of virus used for infection.
- This research hence suggests potential strategies for dealing with persistent viruses like BDV, potentially transforming future therapeutics and disease prevention methods.
Cite This Article
APA
Furrer E, Bilzer T, Stitz L, Planz O.
(2001).
High-dose Borna disease virus infection induces a nucleoprotein-specific cytotoxic T-lymphocyte response and prevention of immunopathology.
J Virol, 75(23), 11700-11708.
https://doi.org/10.1128/JVI.75.23.11700-11708.2001 Publication
Researcher Affiliations
- Institut für Immunologie, Bundesforschungsanstalt für Viruskrankheiten der Tiere, Tübingen, Germany.
MeSH Terms
- Animals
- Borna Disease / immunology
- Dose-Response Relationship, Immunologic
- Female
- Male
- Nucleoproteins / immunology
- Rats
- Rats, Inbred Lew
- T-Lymphocytes, Cytotoxic / immunology
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