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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

Publications

  • PLoS Pathog. 2019 Aug 1;15(8):e1007873. doi: 10.1371/journal.ppat.1007873. eCollection 2019 Aug.

Human bornavirus research: Back on track!

Rubbenstroth D, Schlottau K, Schwemmle M, Rissland J, Beer M.

pubmed

  • N Engl J Med. 2018 Oct 4;379(14):1377-1379. doi: 10.1056/NEJMc1803115.

Fatal Encephalitic Borna Disease Virus 1 in Solid-Organ Transplant Recipients.

Schlottau K, Forth L, Angstwurm K, Höper D, Zecher D, Liesche F, Hoffmann B, Kegel V, Seehofer D, Platen S, Salzberger B, Liebert UG, Niller HH, Schmidt B, Matiasek K, Riemenschneider MJ, Brochhausen C, Banas B, Renders L, Moog P, Wunderlich S, Seifert CL, Barreiros A, Rahmel A, Weiss J, Tappe D, Herden C, Schmidt-Chanasit J, Schwemmle M, Rubbenstroth D, Schlegel J, Pietsch C, Hoffmann D, Jantsch J, Beer M.

pubmed

  • Arch Virol 2015 Feb;160(2):621-32. doi: 10.1007/s00705-014-2276-z. Epub 2014 Dec 2.

Taxonomic reorganization of the family Bornaviridae.

Kuhn JH, Dürrwald R, Bào Y, Briese T, Carbone K, Clawson AN, deRisi JL, Garten W, Jahrling PB, Kolodziejek J, Rubbenstroth D, Schwemmle M, Stenglein M, Tomonaga K, Weissenböck H, Nowotny N.

pubmed

  • Sci Rep. 2016 May 13;6:25873. doi: 10.1038/srep25873.

An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus.

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

>PubMed

  • Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1899-904. doi: 10.1073/pnas.1214939110. Epub 2013 Jan 14.

Borna disease virus-induced neuronal degeneration dependent on host genetic background and prevented by soluble factors.

Wu YJ, Schulz H, Lin CC, Saar K, Patone G, Fischer H, Hübner N, Heimrich B, Schwemmle M.

>PubMed

  • Cell Mol Life Sci. 2013 Nov;70(22):4399-410. doi: 10.1007/s00018-013-1402-5. Epub 2013 Jun 23.

Absence of a robust innate immune response in rat neurons facilitates persistent infection of Borna disease virus in neuronal tissue.

Lin CC, Wu YJ, Heimrich B, Schwemmle M.

>PubMed

  • J Virol. 2013 Nov;87(22):12339-48. doi: 10.1128/JVI.01127-13. Epub 2013 Sep 11

Analysis of borna disease virus trafficking in live infected cells by using a virus encoding a tetracysteine-tagged p protein.

Charlier CM, Wu YJ, Allart S, Malnou CE, Schwemmle M, Gonzalez-Dunia D.

>PubMed

  • Mol Psychiatry 17: 486-493 (2012)

Absence of evidence for bornavirus infection ins schizophrenia, bipolar disorder and major depressive disorder

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.

>PubMed

  • Cell Host Microbe 11: 492-503 (2012)

Bornavirus closely associates and segregates with host chromosomes to ensure persistent intranuclear infection

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.

>PubMed

  • Cell Tissue Res 344: 13-6 (2011)

Viral interference with neuronal integrity: what can we learn from the Borna disease virus?

Schwemmle M, Heimrich B.

>PubMed

  • Arch Virol 155: 789-93 (2010)

Protein kinase C-dependent phosphorylation of Borna disease virus P protein is required for efficient viral spread

Schmid, S., P. Metz, C. M. Prat, D. Gonzalez-Dunia, and M. Schwemmle

>PubMed

  • PLoS Pathog 5: e1000425 (2009)

Mutation of the protein kinase C site in borna disease virus phosphoprotein abrogates viral interference with neuronal signaling and restores normal synaptic activity

Prat, C. M., S. Schmid, F. Farrugia, N. Cenac, G. Le Masson, M. Schwemmle, and D. Gonzalez-Dunia.

>PubMed

  • Cell Tissue Res 338: 179-90 (2009)

Borna disease virus infection alters synaptic input of neurons in rat dentate gyrus

Heimrich, B., D. A. Hesse, Y. J. Wu, S. Schmid, and M. Schwemmle.

>PubMed

  • J Virol 81: 743-9 (2007)

Borna disease virus matrix protein is an integral component of the viral ribonucleoprotein complex that does not interfere with polymerase activity

Chase, G., D. Mayer, A. Hildebrand, R. Frank, Y. Hayashi, K. Tomonaga, and M. Schwemmle.

>PubMed

 

  • J Virol 79: 11716-23 (2005)

Borna disease virus replication in organotypic hippocampal slice cultures from rats results in selective damage of dentate granule cells

Mayer, D., H. Fischer, U. Schneider, B. Heimrich, and M. Schwemmle.

>PubMed

  • Proteomics 5: 483-7 (2005)

Isolation of viral ribonucleoprotein complexes from infected cells by tandem affinity purification

Mayer, D., S. Baginsky, and M. Schwemmle.

>PubMed

  • Virus Res 111: 224-34 (2005)

Borna disease virus interference with neuronal plasticity

Gonzalez-Dunia, D., R. Volmer, D. Mayer, and M. Schwemmle.

>PubMed

  • J Virol 79: 11716-23 (2005)

Borna disease virus replication in organotypic hippocampal slice cultures from rats results in selective damage of dentate granule cells

Mayer, D., H. Fischer, U. Schneider, B. Heimrich, and M. Schwemmle.

>PubMed

  • Proteomics 5: 483-7 (2005)

Isolation of viral ribonucleoprotein complexes from infected cells by tandem affinity purification

Mayer, D., S. Baginsky, and M. Schwemmle.

>PubMed

  • Virus Res 111: 224-34 (2005)

Borna disease virus interference with neuronal plasticity

Gonzalez-Dunia, D., R. Volmer, D. Mayer, and M. Schwemmle.

>PubMed

  • Virus Res. 2005 Aug;111(2):224-34.

Borna disease virus interference with neuronal plasticity.

Gonzalez-Dunia D1, Volmer R, Mayer D, Schwemmle M.

pubmed

  • J Biol Chem. 2004 Dec 31;279(53):55290-6. Epub 2004 Oct 27.

Overlap of interaction domains indicates a central role of the P protein in assembly and regulation of the Borna disease virus polymerase complex.

Schneider U, Blechschmidt K, Schwemmle M, Staeheli P.

pubmed

  • Mol Divers. 2004;8(3):247-50.

The use of peptide arrays for the characterization of monospecific antibody repertoires from polyclonal sera of psychiatric patients suspected of infection by Borna Disease Virus.

Schwemmle M, Billich C.

pubmed

  • J Virol. 2003 Nov;77(21):11781-9.

Active borna disease virus polymerase complex requires a distinct nucleoprotein-to-phosphoprotein ratio but no viral X protein.

Schneider U, Naegele M, Staeheli P, Schwemmle M.

pubmed

  • J Virol. 2003 Apr;77(7):4283-90.

Selective virus resistance conferred by expression of Borna disease virus nucleocapsid components.

Geib T, Sauder C, Venturelli S, Hässler C, Staeheli P, Schwemmle M.

pubmed

  • Arch Virol. 2003 Jan;148(1):45-63.

Identification of differentially expressed genes in brains of newborn Borna disease virus-infected rats in the absence of inflammation.

Jehle C, Herpfer I, Rauer M, Schwemmle M, Sauder C.

pubmed

  • Biol Psychiatry. 2002 Jun 15;51(12):979-87.

High-avidity human serum antibodies recognizing linear epitopes of Borna disease virus proteins.

Billich C, Sauder C, Frank R, Herzog S, Bechter K, Takahashi K, Peters H, Staeheli P, Schwemmle M.

pubmed

  • Lancet Infect Dis. 2001 Aug;1(1):46-52.

Borna disease virus infection in psychiatric patients: are we on the right track?

Schwemmle M.

pubmed

  • J Gen Virol. 2001 Nov;82(Pt 11):2681-90.

Conservation of coding potential and terminal sequences in four different isolates of Borna disease virus.

Pleschka S, Staeheli P, Kolodziejek J, Richt JA, Nowotny N, Schwemmle M.

pubmed

  • J Gen Virol. 2000 Sep;81(Pt 9):2123-35.

Epidemiology of Borna disease virus.

Staeheli P, Sauder C, Hausmann J, Ehrensperger F, Schwemmle M.

pubmed

  • J Virol. 2000 Sep;74(17):7878-83.

Sequence variability of Borna disease virus: resistance to superinfection may contribute to high genome stability in persistently infected cells.

Formella S, Jehle C, Sauder C, Staeheli P, Schwemmle M.

pubmed

  • J Gen Virol. 2000 Aug;81(Pt 8):1947-54.

Authentic Borna disease virus transcripts are spliced less efficiently than cDNA-derived viral RNAs.

Jehle C, Lipkin WI, Staeheli P, Marion RM, Schwemmle M.

pubmed

  • J Virol. 2000 Jun;74(12):5655-8.

Isolation and characterization of a new subtype of Borna disease virus.

Nowotny N, Kolodziejek J, Jehle CO, Suchy A, Staeheli P, Schwemmle M.

pubmed

  • Lancet. 1999 Dec 4;354(9194):1973-4.

Sequence similarities between human bornavirus isolates and laboratory strains question human origin.

Schwemmle M, Jehle C, Formella S, Staeheli P.

pubmed

  • Arch Virol. 1999;144(4):835-40.

Progress and controversy in Bornavirus research: a meeting report.

Schwemmle M.

pubmed

  • J Gen Virol. 1999 Jan;80 ( Pt 1):97-100.

Characterization of the major nuclear localization signal of the Borna disease virus phosphoprotein.

Schwemmle M, Jehle C, Shoemaker T, Lipkin WI.

pubmed

  • J Biol Chem. 1998 Apr 10;273(15):9007-12.

Interactions of the borna disease virus P, N, and X proteins and their functional implications.

Schwemmle M, Salvatore M, Shi L, Richt J, Lee CH, Lipkin WI.

pubmed

  • J Virol. 1998 May;72(5):4379-86.

Borna disease virus-induced neurological disorder in mice: infection of neonates results in immunopathology.

Hallensleben W, Schwemmle M, Hausmann J, Stitz L, Volk B, Pagenstecher A, Staeheli P.

pubmed

  • J Virol. 1997 Nov;71(11):8940-5.

Implication of a cis-acting element in the cytoplasmic accumulation of unspliced Borna disease virus RNAs.

Schneider PA, Schwemmle M, Lipkin WI.

pubmed

  • J Biol Chem. 1997 Aug 29;272(35):21818-23.

Borna disease virus P-protein is phosphorylated by protein kinase Cepsilon and casein kinase II.

Schwemmle M, De B, Shi L, Banerjee A, Lipkin WI.

pubmed

  • Lancet. 1997 Jun 21;349(9068):1813-4.

Borna disease virus in brains of North American and European people with schizophrenia and bipolar disorder. Bornavirus Study Group.

Salvatore M, Morzunov S, Schwemmle M, Lipkin WI.

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