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Journal of virology2001; 75(23); 11700-11708; doi: 10.1128/JVI.75.23.11700-11708.2001

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

ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 75
Issue: 23
Pages: 11700-11708

Researcher Affiliations

Furrer, E
  • Institut für Immunologie, Bundesforschungsanstalt für Viruskrankheiten der Tiere, Tübingen, Germany.
Bilzer, T
    Stitz, L
      Planz, O

        MeSH Terms

        • Animals
        • Borna Disease / immunology
        • Dose-Response Relationship, Immunologic
        • Female
        • Male
        • Nucleoproteins / immunology
        • Rats
        • Rats, Inbred Lew
        • T-Lymphocytes, Cytotoxic / immunology

        References

        This article includes 40 references
        1. Amsterdam JD, Winokur A, Dyson W, Herzog S, Gonzalez F, Rott R, Koprowski H. Borna disease virus. A possible etiologic factor in human affective disorders?. Arch Gen Psychiatry 1985 Nov;42(11):1093-6.
        2. Bilzer T, Stitz L. Immune-mediated brain atrophy. CD8+ T cells contribute to tissue destruction during borna disease.. J Immunol 1994 Jul 15;153(2):818-23.
          pubmed: 7912707
        3. Bilzer T, Stitz L. Immunopathogenesis of virus diseases affecting the central nervous system.. Crit Rev Immunol 1996;16(2):145-222.
        4. Bode L, Dürrwald R, Ludwig H. Borna virus infections in cattle associated with fatal neurological disease.. Vet Rec 1994 Sep 17;135(12):283-4.
          pubmed: 7817508doi: 10.1136/vr.135.12.283google scholar: lookup
        5. Bode L, Zimmermann W, Ferszt R, Steinbach F, Ludwig H. Borna disease virus genome transcribed and expressed in psychiatric patients.. Nat Med 1995 Mar;1(3):232-6.
          pubmed: 7585039doi: 10.1038/nm0395-232google scholar: lookup
        6. Caplazi P, Waldvogel A, Stitz L, Braun U, Ehrensperger F. Borna disease in naturally infected cattle.. J Comp Pathol 1994 Jul;111(1):65-72.
          pubmed: 7962728doi: 10.1016/s0021-9975(05)80112-4google scholar: lookup
        7. Cole GA, Nathanson N, Prendergast RA. Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease.. Nature 1972 Aug 11;238(5363):335-7.
          pubmed: 4561841doi: 10.1038/238335a0google scholar: lookup
        8. 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.
          pubmed: 2085093doi: 10.1007/bf00662636google scholar: lookup
        9. Furrer E, Bilzer T, Stitz L, Planz O. Neutralizing antibodies in persistent borna disease virus infection: prophylactic effect of gp94-specific monoclonal antibodies in preventing encephalitis.. J Virol 2001 Jan;75(2):943-51.
        10. Hatalski CG, Hickey WF, Lipkin WI. Evolution of the immune response in the central nervous system following infection with Borna disease virus.. J Neuroimmunol 1998 Oct 1;90(2):137-42.
          pubmed: 9817441doi: 10.1016/s0165-5728(98)00076-9google scholar: lookup
        11. Hatalski CG, Hickey WF, Lipkin WI. Humoral immunity in the central nervous system of Lewis rats infected with Borna disease virus.. J Neuroimmunol 1998 Oct 1;90(2):128-36.
          pubmed: 9817440doi: 10.1016/s0165-5728(98)00066-6google scholar: lookup
        12. Herzog S, Rott R. Replication of Borna disease virus in cell cultures.. Med Microbiol Immunol 1980;168(3):153-8.
          pubmed: 6772932doi: 10.1007/bf02122849google scholar: lookup
        13. Kishi M, Arimura Y, Ikuta K, Shoya Y, Lai PK, Kakinuma M. Sequence variability of Borna disease virus open reading frame II found in human peripheral blood mononuclear cells.. J Virol 1996 Jan;70(1):635-40.
          pmc: PMC189858pubmed: 8523585doi: 10.1128/jvi.70.1.635-640.1996google scholar: lookup
        14. Ludwig H, Thein P. Demonstration of specific antibodies in the central nervous system of horses naturally infected with Borna disease virus.. Med Microbiol Immunol 1977 Dec 27;163(4):215-26.
          pubmed: 604728doi: 10.1007/bf02125505google scholar: lookup
        15. Lundgren AL, Lindberg R, Ludwig H, Gosztonyi G. Immunoreactivity of the central nervous system in cats with a Borna disease-like meningoencephalomyelitis (staggering disease).. Acta Neuropathol 1995;90(2):184-93.
          pmc: PMC7086677pubmed: 7484095doi: 10.1007/bf00294319google scholar: lookup
        16. Malkinson M, Weisman Y, Perl S, Ashash E. A Borna-like disease of ostriches in Israel.. Curr Top Microbiol Immunol 1995;190:31-8.
          pubmed: 7789149doi: 10.1007/978-3-642-78618-1_3google scholar: lookup
        17. Moskophidis D, Lechner F, Pircher H, Zinkernagel RM. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells.. Nature 1993 Apr 22;362(6422):758-61.
          pubmed: 8469287doi: 10.1038/362758a0google scholar: lookup
        18. Nakamura Y, Takahashi H, Shoya Y, Nakaya T, Watanabe M, Tomonaga K, Iwahashi K, Ameno K, Momiyama N, Taniyama H, Sata T, Kurata T, de la Torre JC, Ikuta K. Isolation of Borna disease virus from human brain tissue.. J Virol 2000 May;74(10):4601-11.
        19. Narayan O, Herzog S, Frese K, Scheefers H, Rott R. Pathogenesis of Borna disease in rats: immune-mediated viral ophthalmoencephalopathy causing blindness and behavioral abnormalities.. J Infect Dis 1983 Aug;148(2):305-15.
          pubmed: 6604114doi: 10.1093/infdis/148.2.305google scholar: lookup
        20. Nöske K, Bilzer T, Planz O, Stitz L. Virus-specific CD4+ T cells eliminate borna disease virus from the brain via induction of cytotoxic CD8+ T cells.. J Virol 1998 May;72(5):4387-95.
        21. Oldach D, Zink MC, Pyper JM, Herzog S, Rott R, Narayan O, Clements JE. Induction of protection against Borna disease by inoculation with high-dose-attenuated Borna disease virus.. Virology 1995 Jan 10;206(1):426-34.
          pubmed: 7831798doi: 10.1016/s0042-6822(95)80058-1google scholar: lookup
        22. Peters M, Vierling J, Gershwin ME, Milich D, Chisari FV, Hoofnagle JH. Immunology and the liver.. Hepatology 1991 May;13(5):977-94.
          pubmed: 2030002
        23. Planz O, Bilzer T, Sobbe M, Stitz L. Lysis of major histocompatibility complex class I-bearing cells in Borna disease virus-induced degenerative encephalopathy.. J Exp Med 1993 Jul 1;178(1):163-74.
          pmc: PMC2191065pubmed: 8315376doi: 10.1084/jem.178.1.163google scholar: lookup
        24. Planz O, Bilzer T, Stitz L. Immunopathogenic role of T-cell subsets in Borna disease virus-induced progressive encephalitis.. J Virol 1995 Feb;69(2):896-903.
          pmc: PMC188657pubmed: 7815558doi: 10.1128/jvi.69.2.896-903.1995google scholar: lookup
        25. Planz O, Dumrese T, Hulpusch S, Schirle M, Stevanovic S, Stitz L. A naturally processed rat major histocompatibility complex class I-associated viral peptide as target structure of borna disease virus-specific CD8+ T cells.. J Biol Chem 2001 Apr 27;276(17):13689-94.
          pubmed: 11278578doi: 10.1074/jbc.m009889200google scholar: lookup
        26. Planz O, Rentzsch C, Batra A, Rziha HJ, Stitz L. Persistence of Borna disease virus-specific nucleic acid in blood of psychiatric patient.. Lancet 1998 Aug 22;352(9128):623.
          pubmed: 9746029doi: 10.1016/s0140-6736(05)79577-5google scholar: lookup
        27. Planz O, Stitz L. Borna disease virus nucleoprotein (p40) is a major target for CD8(+)-T-cell-mediated immune response.. J Virol 1999 Feb;73(2):1715-8.
        28. Richt JA, Schmeel A, Frese K, Carbone KM, Narayan O, Rott R. Borna disease virus-specific T cells protect against or cause immunopathological Borna disease.. J Exp Med 1994 May 1;179(5):1467-73.
          pmc: PMC2191504pubmed: 7909324doi: 10.1084/jem.179.5.1467google scholar: lookup
        29. Richt JA, Stitz L, Wekerle H, Rott R. Borna disease, a progressive meningoencephalomyelitis as a model for CD4+ T cell-mediated immunopathology in the brain.. J Exp Med 1989 Sep 1;170(3):1045-50.
          pmc: PMC2189432pubmed: 2788704doi: 10.1084/jem.170.3.1045google scholar: lookup
        30. Rott R, Becht H. Natural and experimental Borna disease in animals.. Curr Top Microbiol Immunol 1995;190:17-30.
          pubmed: 7789148doi: 10.1007/978-3-642-78618-1_2google scholar: lookup
        31. Rott R, Herzog S, Fleischer B, Winokur A, Amsterdam J, Dyson W, Koprowski H. Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders.. Science 1985 May 10;228(4700):755-6.
          pubmed: 3922055doi: 10.1126/science.3922055google scholar: lookup
        32. Sobbe M, Bilzer T, Gommel S, Nöske K, Planz O, Stitz L. Induction of degenerative brain lesions after adoptive transfer of brain lymphocytes from Borna disease virus-infected rats: presence of CD8+ T cells and perforin mRNA.. J Virol 1997 Mar;71(3):2400-7.
        33. Stitz L, Dietzschold B, Carbone KM. Immunopathogenesis of Borna disease.. Curr Top Microbiol Immunol 1995;190:75-92.
          pubmed: 7789151doi: 10.1007/978-3-642-78618-1_5google scholar: lookup
        34. 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.
        35. Stitz L, Rott R. Borna disease virus (Bornaviridae). Encyclopedia of virology 1999;pp. 167–173.
        36. Thiedemann N, Presek P, Rott R, Stitz L. Antigenic relationship and further characterization of two major Borna disease virus-specific proteins.. J Gen Virol 1992 May;73 ( Pt 5):1057-64.
          pubmed: 1588316doi: 10.1099/0022-1317-73-5-1057google scholar: lookup
        37. Waltrip RW 2nd, Buchanan RW, Carpenter WT Jr, Kirkpatrick B, Summerfelt A, Breier A, Rubin SA, Carbone KM. Borna disease virus antibodies and the deficit syndrome of schizophrenia.. Schizophr Res 1997 Feb 28;23(3):253-7.
          pubmed: 9075304doi: 10.1016/s0920-9964(96)00114-4google scholar: lookup
        38. Weissenböck H, Nowotny N, Caplazi P, Kolodziejek J, Ehrensperger F. Borna disease in a dog with lethal meningoencephalitis.. J Clin Microbiol 1998 Jul;36(7):2127-30.
        39. Zinkernagel RM. Virus-induced immunopathology. Viral pathogenesis 1997;pp. 163–179.
        40. Zinkernagel RM, Haenseler E, Leist T, Cerny A, Hengartner H, Althage A. T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay?. J Exp Med 1986 Oct 1;164(4):1075-92.
          pmc: PMC2188412pubmed: 3489805doi: 10.1084/jem.164.4.1075google scholar: lookup

        Citations

        This article has been cited 9 times.
        1. Eidenschink L, Knoll G, Tappe D, Offner R, Drasch T, Ehrl Y, Banas B, Banas MC, Niller HH, Gessner A, Köstler J, Lampl BMJ, Pregler M, Völkl M, Kunkel J, Neumann B, Angstwurm K, Schmidt B, Bauswein M. IFN-γ-Based ELISpot as a New Tool to Detect Human Infections with Borna Disease Virus 1 (BoDV-1): A Pilot Study.. Viruses 2023 Jan 10;15(1).
          doi: 10.3390/v15010194pubmed: 36680234google scholar: lookup
        2. Dürrwald R, Kolodziejek J, Oh DY, Herzog S, Liebermann H, Osterrieder N, Nowotny N. Vaccination against Borna Disease: Overview, Vaccine Virus Characterization and Investigation of Live and Inactivated Vaccines.. Viruses 2022 Dec 2;14(12).
          doi: 10.3390/v14122706pubmed: 36560710google scholar: lookup
        3. More S, Bøtner A, Butterworth A, Calistri P, Depner K, Edwards S, Garin-Bastuji B, Good M, Gortázar Schmidt C, Michel V, Miranda MA, Nielsen SS, Raj M, Sihvonen L, Spoolder H, Stegeman JA, Thulke HH, Velarde A, Willeberg P, Winckler C, Baldinelli F, Broglia A, Dhollander S, Beltrán-Beck B, Kohnle L, Bicout D. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): Borna disease.. EFSA J 2017 Jul;15(7):e04951.
          doi: 10.2903/j.efsa.2017.4951pubmed: 32625602google scholar: lookup
        4. Bulbow H, Wu J, Turner D, McEntire M, Tizard I. Campylobacter colonization is not associated with proventricular dilatation disease in psittacines.. Vet Med (Auckl) 2017;8:37-40.
          doi: 10.2147/VMRR.S137213pubmed: 30050854google scholar: lookup
        5. Kinnunen PM, Inkeroinen H, Ilander M, Kallio ER, Heikkilä HP, Koskela E, Mappes T, Palva A, Vaheri A, Kipar A, Vapalahti O. Intracerebral Borna disease virus infection of bank voles leading to peripheral spread and reverse transcription of viral RNA.. PLoS One 2011;6(8):e23622.
          doi: 10.1371/journal.pone.0023622pubmed: 21935357google scholar: lookup
        6. Perez M, Clemente R, Robison CS, Jeetendra E, Jayakar HR, Whitt MA, de la Torre JC. Generation and characterization of a recombinant vesicular stomatitis virus expressing the glycoprotein of Borna disease virus.. J Virol 2007 Jun;81(11):5527-36.
          doi: 10.1128/JVI.02586-06pubmed: 17376911google scholar: lookup
        7. Hausmann J, Pagenstecher A, Baur K, Richter K, Rziha HJ, Staeheli P. CD8 T cells require gamma interferon to clear borna disease virus from the brain and prevent immune system-mediated neuronal damage.. J Virol 2005 Nov;79(21):13509-18.
        8. Bourteele S, Oesterle K, Pleschka S, Unterstab G, Ehrhardt C, Wolff T, Ludwig S, Planz O. Constitutive activation of the transcription factor NF-kappaB results in impaired borna disease virus replication.. J Virol 2005 May;79(10):6043-51.
        9. Hashimoto Y, Chen HS, Cunningham C, Malik TH, Lai PK. Two major histocompatibility complex class I-restricted epitopes of the Borna disease virus p10 protein identified by cytotoxic T lymphocytes induced by DNA-based immunization.. J Virol 2003 May;77(10):6076-81.