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Institute of Virology

Borna Disease Virus

Borna disease virus (BDV) is an enveloped virus with an RNA genome of negative polarity which replicates in the nucleus of the infected cell. BDV can persistently infect neurons of the central nervous system without causing general cell death, reflecting a unique adaptation to the brain. This adaptation of BDV is accompanied by subtle consequences for infected neurons, including changes in the neuronal and synaptic plasticity and epigenetic alterations. However, BDV can also cause an immune-mediated pathology of the brain in various animal species; however, there is no evidence so far that BDV can also infect humans. Intriguingly, zoonotic transmission of a related BDV, the Variegated Squirrel Bornavirus, from squirrels to humans was recently reported to cause fatal encephalitis. The requirements of these newly identified bornaviruses to cross the species barrier are currently studied in a newly formed Zoonotic Bornavirus Consortium (ZooBoCo) funded by the Bundesministerium für Bildung und Forschung.

Infection of hippocampus slice cultures with Borna Disease Virus (BDV).
Left panel: Hippocampus slice cultures obtained from a newborn Lewis rat was infected with BDV and stained 2 weeks after infection for BDV (green), calbindin (red), which is a maker for dentate granule cells.. mf, mossy fiber, dgc, dentate granule cells.
Right panel: Dissociated primary neuronal cultures were obtained from the cortex of newborn Lewis rats. They were infected with BDV for 1 week and subjected to immunofluorescence analysis by using specific antibodies against BDV (blue) and Map2 (red), a specific marker of neurons. Bar 40 μm.

Press Release:

Forschungsverbund nimmt gefährliche Bornaviren ins Visier

Selected References:

 

  1. Gonzalez-Dunia, D., R. Volmer, D. Mayer, and M. Schwemmle.
    Borna disease virus interference with neuronal plasticity

    Virus Res 111: 224-34 (2005)
    >PubMed
  2. Mayer, D., S. Baginsky, and M. Schwemmle.
    Isolation of viral ribonucleoprotein complexes from infected cells by tandem affinity purification

    Proteomics 5: 483-7 (2005)
    >PubMed
  3. Mayer, D., H. Fischer, U. Schneider, B. Heimrich, and M. Schwemmle.
    Borna disease virus replication in organotypic hippocampal slice cultures from rats results in selective damage of dentate granule cells

    J Virol 79: 11716-23 (2005)
    >PubMed
  4. Chase, G., D. Mayer, A. Hildebrand, R. Frank, Y. Hayashi, K. Tomonaga, and M. Schwemmle.
    Borna disease virus matrix protein is an integral component of the viral ribonucleoprotein complex that does not interfere with polymerase activity

    J Virol 81: 743-9 (2007)
    >PubMed
  5. Heimrich, B., D. A. Hesse, Y. J. Wu, S. Schmid, and M. Schwemmle.
    Borna disease virus infection alters synaptic input of neurons in rat dentate gyrus

    Cell Tissue Res 338: 179-90 (2009)
    >PubMed
  6. Prat, C. M., S. Schmid, F. Farrugia, N. Cenac, G. Le Masson, M. Schwemmle, and D. Gonzalez-Dunia.
    Mutation of the protein kinase C site in borna disease virus phosphoprotein abrogates viral interference with neuronal signaling and restores normal synaptic activity

    PLoS Pathog 5: e1000425 (2009)
    >PubMed
  7. Schmid, S., P. Metz, C. M. Prat, D. Gonzalez-Dunia, and M. Schwemmle
    Protein kinase C-dependent phosphorylation of Borna disease virus P protein is required for efficient viral spread

    Arch Virol 155: 789-93 (2010)
    >PubMed
  8. Schwemmle M, Heimrich B.
    Viral interference with neuronal integrity: what can we learn from the Borna disease virus?

    Cell Tissue Res 344: 13-6 (2011)
    >PubMed
  9. Matsumoto, Y., Hayashi Y., Omori, H., Honda, T., Daito, T., Horie, M., Ikuta, K., Fujino, K., Nakamura, S., Schneider, U., Chase, G., Yoshimori, T., Schwemmle, M., Tomonaga, K.
    Bornavirus closely associates and segregates with host chromosomes to ensure persistent intranuclear infection

    Cell Host Microbe 11: 492-503 (2012)
    >PubMed
  10. Hornig, M., Briese, T., Licinio, J., Khabbaz, R.F., Altshuler, L.L., Potkin, S.G., Schwemmle, M., Siemetzki, U., Mintz, J., Honkavuori, K., Kraemer, H.C., Egan, M.F., Whybrow, P.C., Bunney, W.E., Lipkin, W.I.
    Absence of evidence for bornavirus infection ins schizophrenia, bipolar disorder and major depressive disorder

    Mol Psychiatry 17: 486-493 (2012)
    >PubMed
  11. Charlier CM, Wu YJ, Allart S, Malnou CE, Schwemmle M, Gonzalez-Dunia D.
    Analysis of borna disease virus trafficking in live infected cells by using a virus encoding a tetracysteine-tagged p protein.

    J Virol. 2013 Nov;87(22):12339-48. doi: 10.1128/JVI.01127-13. Epub 2013 Sep 11
    >PubMed
  12. Lin CC, Wu YJ, Heimrich B, Schwemmle M.
    Absence of a robust innate immune response in rat neurons facilitates persistent infection of Borna disease virus in neuronal tissue.

    Cell Mol Life Sci. 2013 Nov;70(22):4399-410. doi: 10.1007/s00018-013-1402-5. Epub 2013 Jun 23.
    PMID:
    >PubMed
  13. Wu YJ, Schulz H, Lin CC, Saar K, Patone G, Fischer H, Hübner N, Heimrich B, Schwemmle M.
    Borna disease virus-induced neuronal degeneration dependent on host genetic background and prevented by soluble factors.

    Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1899-904. doi: 10.1073/pnas.1214939110. Epub 2013 Jan 14.
    PMID:
    >PubMed
  14. Horie M, Kobayashi Y, Honda T, Fujino K, Akasaka T, Kohl C, Wibbelt G, Mühldorfer K, Kurth A, Müller MA, Corman VM, Gillich N, Suzuki Y, Schwemmle M, Tomonaga K
    An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus.
    Sci Rep. 2016 May 13;6:25873. doi: 10.1038/srep25873.
    >PubMed

 

 


Institut für Virologie

Hermann-Herder-Strasse 11
D-79104 Freiburg

Ärztlicher Direktor

Prof. Dr. med. Hartmut Hengel
hartmut.hengel@uniklinik-freiburg.de

Team Leader:

Martin Schwemmle
(Ph.D., Professor)
Phone: +49 761 203 6526
Fax: +49 761 203 6639