Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 27, Number 5—May 2021
Research

Active Case Finding of Current Bornavirus Infections in Human Encephalitis Cases of Unknown Etiology, Germany, 2018–2020

Philip Eisermann1, Dennis Rubbenstroth1, Daniel Cadar, Corinna Thomé-Bolduan, Petra Eggert, Alexander Schlaphof, Frank Leypoldt, Martin Stangel, Thorsten Fortwängler, Florian Hoffmann, Andreas Osterman, Sabine Zange, Hans-Helmut Niller, Klemens Angstwurm, Kirsten Pörtner, Christina Frank, Hendrik Wilking, Martin Beer, Jonas Schmidt-Chanasit, and Dennis TappeComments to Author 
Author affiliations: Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Germany (P. Eisermann, D. Cadar, C. Thomé-Bolduan, P. Eggert, A. Schlaphof, J. Schmidt-Chanasit, D. Tappe); Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany (D. Rubbenstroth, M. Beer); University Medical Center Schleswig-Holstein, Kiel, Germany (F. Leypoldt); Medizinische Hochschule Hannover, Hannover, Germany (M. Stangel); Donau-Isar-Klinikum Deggendorf, Deggendorf, Germany (T. Fortwängler); Ludwig-Maximilians-University, Munich, Germany (F. Hoffmann); Max von Pettenkofer Institute, Munich (A. Osterman); German Center for Infection Research, Munich (A. Osterman); Bundeswehr Institute of Microbiology, Munich (S. Zange); Regensburg University Hospital, Regensburg, Germany (H.-H. Niller, K. Angstwurm); Postgraduate Training for Applied Epidemiology, Berlin, Germany (K. Pörtner); European Centre for Disease Prevention and Control, Stockholm, Sweden (K. Pörtner); Robert Koch Institute, Berlin (K. Pörtner, C. Frank, H. Wilking)

Main Article

Figure 3

Reactivity of samples from BoDV-1- and VSBV-1-infected patients with homologous and heterologous bornavirus P antigens, Germany. Bornavirus indirect immunofluorescence antibody test–positive serum and cerebrospinal fluid samples were tested by using the Euroimmun (https://www.euroimmun.com) line blot with BoDV-1 P and VSBV-1 P antigens (BoDV-1: 52 samples from 14 patients; VSBV-1: 3 samples from 2 patients). Samples originated from patients with laboratory-confirmed BoDV-1 or VSBV-1 infection (2,10–12; this study). Results are indicated as arbitrary units. Dotted line indicates cutoff value of 16 as defined by the manufacturer. BoDV-1, Borna disease virus 1; P, phosphoprotein; VSBV-1, variegated squirrel bornavirus 1.

Figure 3. Reactivity of samples from BoDV-1- and VSBV-1-infected patients with homologous and heterologous bornavirus P antigens, Germany. Bornavirus indirect immunofluorescence antibody test–positive serum and cerebrospinal fluid samples were tested by using the Euroimmun (https://www.euroimmun.com) line blot with BoDV-1 P and VSBV-1 P antigens (BoDV-1: 52 samples from 14 patients; VSBV-1: 3 samples from 2 patients). Samples originated from patients with laboratory-confirmed BoDV-1 or VSBV-1 infection (2,10–12; this study). Results are indicated as arbitrary units. Dotted line indicates cutoff value of 16 as defined by the manufacturer. BoDV-1, Borna disease virus 1; P, phosphoprotein; VSBV-1, variegated squirrel bornavirus 1.

Main Article

References
  1. Hoffmann  B, Tappe  D, Höper  D, Herden  C, Boldt  A, Mawrin  C, et al. A variegated squirrel bornavirus associated with fatal human encephalitis. N Engl J Med. 2015;373:154–62. DOIPubMedGoogle Scholar
  2. Schlottau  K, Forth  L, Angstwurm  K, Höper  D, Zecher  D, Liesche  F, et al. Fatal encephalitic borna disease virus 1 in solid-organ transplant recipients. N Engl J Med. 2018;379:1377–9. DOIPubMedGoogle Scholar
  3. Korn  K, Coras  R, Bobinger  T, Herzog  SM, Lücking  H, Stöhr  R, et al. Fatal encephalitis associated with borna disease virus 1. N Engl J Med. 2018;379:1375–7. DOIPubMedGoogle Scholar
  4. Schlottau  K, Jenckel  M, van den Brand  J, Fast  C, Herden  C, Höper  D, et al. Variegated squirrel bornavirus 1 in squirrels, Germany and the Netherlands. Emerg Infect Dis. 2017;23:477–81. DOIPubMedGoogle Scholar
  5. Schlottau  K, Hoffmann  B, Homeier-Bachmann  T, Fast  C, Ulrich  RG, Beer  M, et al. Multiple detection of zoonotic variegated squirrel bornavirus 1 RNA in different squirrel species suggests a possible unknown origin for the virus. Arch Virol. 2017;162:2747–54. DOIPubMedGoogle Scholar
  6. Tappe  D, Frank  C, Homeier-Bachmann  T, Wilking  H, Allendorf  V, Schlottau  K, et al. Analysis of exotic squirrel trade and detection of human infections with variegated squirrel bornavirus 1, Germany, 2005 to 2018. Euro Surveill. 2019;24:1800483. DOIPubMedGoogle Scholar
  7. Dürrwald  R, Kolodziejek  J, Weissenböck  H, Nowotny  N. The bicolored white-toothed shrew Crocidura leucodon (HERMANN 1780) is an indigenous host of mammalian Borna disease virus. PLoS One. 2014;9:e93659. DOIPubMedGoogle Scholar
  8. Weissenböck  H, Bagó  Z, Kolodziejek  J, Hager  B, Palmetzhofer  G, Dürrwald  R, et al. Infections of horses and shrews with Bornaviruses in Upper Austria: a novel endemic area of Borna disease. Emerg Microbes Infect. 2017;6:e52. DOIPubMedGoogle Scholar
  9. 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;25:1058–65. DOIPubMedGoogle Scholar
  10. Liesche  F, Ruf  V, Zoubaa  S, Kaletka  G, Rosati  M, Rubbenstroth  D, et al. The neuropathology of fatal encephalomyelitis in human Borna virus infection. Acta Neuropathol. 2019;138:653–65. DOIPubMedGoogle Scholar
  11. Tappe  D, Schlottau  K, Cadar  D, Hoffmann  B, Balke  L, Bewig  B, et al. Occupation-associated fatal limbic encephalitis caused by variegated squirrel bornavirus 1, Germany, 2013. Emerg Infect Dis. 2018;24:978–87. DOIPubMedGoogle Scholar
  12. Niller  HH, Angstwurm  K, Rubbenstroth  D, Schlottau  K, Ebinger  A, Giese  S, et al. Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999-2019: an epidemiological investigation. Lancet Infect Dis. 2020;20:467–77. DOIPubMedGoogle Scholar
  13. Coras  R, Korn  K, Kuerten  S, Huttner  HB, Ensser  A. Severe bornavirus-encephalitis presenting as Guillain-Barré-syndrome. Acta Neuropathol. 2019;137:1017–9. DOIPubMedGoogle Scholar
  14. Venkatesan  A, Tunkel  AR, Bloch  KC, Lauring  AS, Sejvar  J, Bitnun  A, et al.; International Encephalitis Consortium. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013;57:1114–28. DOIPubMedGoogle Scholar
  15. Tappe  D, Frank  C, Offergeld  R, Wagner-Wiening  C, Stark  K, Rubbenstroth  D, et al. Low prevalence of Borna disease virus 1 (BoDV-1) IgG antibodies in humans from areas endemic for animal Borna disease of Southern Germany. Sci Rep. 2019;9:20154. DOIPubMedGoogle Scholar
  16. Zimmermann  V, Rinder  M, Kaspers  B, Staeheli  P, Rubbenstroth  D. Impact of antigenic diversity on laboratory diagnosis of Avian bornavirus infections in birds. J Vet Diagn Invest. 2014;26:769–77. DOIPubMedGoogle Scholar
  17. Kolodziejek  J, Dürrwald  R, Herzog  S, Ehrensperger  F, Lussy  H, Nowotny  N. Genetic clustering of Borna disease virus natural animal isolates, laboratory and vaccine strains strongly reflects their regional geographical origin. J Gen Virol. 2005;86:385–98. DOIPubMedGoogle Scholar
  18. Dürrwald  R, Kolodziejek  J, Herzog  S, Nowotny  N. Meta-analysis of putative human bornavirus sequences fails to provide evidence implicating Borna disease virus in mental illness. Rev Med Virol. 2007;17:181–203. DOIPubMedGoogle Scholar
  19. Nobach  D, Bourg  M, Herzog  S, Lange-Herbst  H, Encarnação  JA, Eickmann  M, et al. Shedding of infectious borna disease virus-1 in living bicolored white-toothed shrews. PLoS One. 2015;10:e0137018. DOIPubMedGoogle Scholar
  20. Schulze  V, Große  R, Fürstenau  J, Forth  LF, Ebinger  A, Richter  MT, et al. Borna disease outbreak with high mortality in an alpaca herd in a previously unreported endemic area in Germany. Transbound Emerg Dis. 2020;67:2093–107. DOIPubMedGoogle Scholar
  21. Hornig  M, Briese  T, Licinio  J, Khabbaz  RF, Altshuler  LL, Potkin  SG, et al. Absence of evidence for bornavirus infection in schizophrenia, bipolar disorder and major depressive disorder. Mol Psychiatry. 2012;17:486–93. DOIPubMedGoogle Scholar
  22. Rubbenstroth  D, Schlottau  K, Schwemmle  M, Rissland  J, Beer  M. Human bornavirus research: Back on track! PLoS Pathog. 2019;15:e1007873. DOIPubMedGoogle Scholar
  23. Billich  C, Sauder  C, Frank  R, Herzog  S, Bechter  K, Takahashi  K, et al. High-avidity human serum antibodies recognizing linear epitopes of Borna disease virus proteins. Biol Psychiatry. 2002;51:979–87. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.

Page created: February 08, 2021
Page updated: April 20, 2021
Page reviewed: April 20, 2021
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external