Literature detail

Lethal Borna disease virus 1 infections of humans and animals - in-depth molecular epidemiology and phylogeography.

Arnt Ebinger1 Pauline D Santos1 Florian Pfaff1 Ralf Dürrwald2 Jolanta Kolodziejek3 Kore Schlottau1 Viktoria Ruf4 Friederike Liesche-Starnecker5,6 Armin Ensser7 Klaus Korn7 Reiner Ulrich8 Jenny Fürstenau9 Kaspar Matiasek10 Florian Hansmann8,11 Torsten Seuberlich12 Daniel Nobach13,14 Matthias Müller15 Antonie Neubauer-Juric16 Marcel Suchowski8,16 Markus Bauswein17 Hans-Helmut Niller18 Barbara Schmidt17 Dennis Tappe19 Daniel Cadar19 Timo Homeier-Bachmann20 Viola C Haring21 Kirsten Pörtner22 Christina Frank22 Lars Mundhenk9 Bernd Hoffmann1 Jochen Herms4 Wolfgang Baumgärtner11 Norbert Nowotny3,23 Jürgen Schlegel24 Rainer G Ulrich21 Martin Beer1 Dennis Rubbenstroth25
Affiliations 25 institutions
  1. Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  2. Robert Koch Institute, Department of Infectious Diseases, Unit 17 Influenza and Other Respiratory Viruses, National Reference Centre for Influenza, Berlin, Germany.
  3. Institute of Virology, University of Veterinary Medicine Vienna, Vienna, Austria.
  4. Center for Neuropathology and Prion Research, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
  5. Department of Neuropathology, Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
  6. Pathology, Medical Faculty, University of Augsburg, Augsburg, Germany.
  7. Institute of Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
  8. Institute of Veterinary Pathology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.
  9. Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
  10. Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
  11. Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
  12. Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  13. Institute of Veterinary Pathology, Justus-Liebig-University Giessen, Giessen, Germany.
  14. Chemical and Veterinary Analysis Agency Stuttgart (CVUAS), Fellbach, Germany.
  15. Bavarian Health and Food Safety Authority, Erlangen, Germany.
  16. Bavarian Health and Food Safety Authority, Oberschleißheim, Germany.
  17. Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany.
  18. Institute for Medical Microbiology, Regensburg University, Regensburg, Germany.
  19. Bernhard Nocht-Institute for Tropical Medicine, Hamburg, Germany.
  20. Institute of Epidemiology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  21. Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  22. Robert Koch Institute, Department of Infectious Disease Epidemiology, Berlin, Germany.
  23. Department of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
  24. Department of Neuropathology, School of Medicine, Institute of Pathology, Technical University Munich, Munich, Germany.
  25. Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. [email protected].
PMID 39256401 2024 Nat Commun eng epublish
PubMed DOI Browse context

Article

Publication summary

Borna disease virus 1 (BoDV-1) is the causative agent of Borna disease, a fatal neurologic disorder of domestic mammals and humans, resulting from spill-over infection from its natural reservoir host, the bicolored white-toothed shrew (Crocidura leucodon). The known BoDV-1-endemic area is remarkably restricted to parts of Germany, Austria, Switzerland and Liechtenstein. To gain comprehensive data on its occurrence, we analysed diagnostic material from suspected BoDV-1-induced encephalitis cases based on clinical and/or histopathological diagnosis. BoDV-1 infection was confirmed by RT-qPCR in 207 domestic mammals, 28 humans and seven wild shrews. Thereby, this study markedly raises the number of published laboratory-confirmed human BoDV-1 infections and provides a first comprehensive summary. Generation of 136 new BoDV-1 genome sequences from animals and humans facilitated an in-depth phylogeographic analysis, allowing for the definition of risk areas for zoonotic BoDV-1 transmission and facilitating the assessment of geographical infection sources. Consistent with the low mobility of its reservoir host, BoDV-1 sequences showed a remarkable geographic association, with individual phylogenetic clades occupying distinct areas. The closest genetic relatives of most human-derived BoDV-1 sequences were located at distances of less than 40 km, indicating that spill-over transmission from the natural reservoir usually occurs in the patient´s home region.

Borna Disease Borna disease virus Molecular Epidemiology Phylogeny Phylogeography Shrews Adult Animals Austria Disease Reservoirs Female Genome, Viral Germany Humans Male Middle Aged Switzerland Zoonoses

Structured evidence records

Evidence records

6 total
2 records
Extraction confidence 0.94
Key finding

Phylogeographic analysis of 136 new BoDV-1 genome sequences from humans and animals revealed distinct geographic clades linked to limited mobility of the shrew reservoir and local spillover sources.

Virus
Location
Not specified
Supporting text

Generation of 136 new BoDV-1 genome sequences from animals and humans facilitated an in-depth phylogeographic analysis, allowing for the definition of risk areas for zoonotic BoDV-1 transmission ... BoDV-1 sequences showed a remarkable geographic association, with individual phylogenetic clades occupying distinct areas.

Genes or proteins
whole genome
Analysis methods
phylogeographic analysis; phylogenetic analysis
Extraction confidence 0.94
Key finding

Phylogeographic analysis of animal-derived BoDV-1 genomes showed regionally distinct clades consistent with limited dispersal of the bicolored white-toothed shrew reservoir.

Virus
Host
Location
Not specified
Supporting text

Generation of 136 new BoDV-1 genome sequences from animals and humans facilitated an in-depth phylogeographic analysis, allowing for the definition of risk areas for zoonotic BoDV-1 transmission ... BoDV-1 sequences showed a remarkable geographic association, with individual phylogenetic clades occupying distinct areas.

Genes or proteins
whole genome
Analysis methods
phylogeographic analysis; phylogenetic analysis
2 records
Extraction confidence 0.83
Key finding

RT-qPCR and genomic sequencing confirmed Borna disease virus 1 infections in multiple host species across Germany, Austria, Switzerland, and Liechtenstein, representing molecular surveillance of animal and human hosts.

Virus
Host
Location
Supporting text

BoDV-1 infection was confirmed by RT-qPCR in 207 domestic mammals, 28 humans and seven wild shrews. Generation of 136 new BoDV-1 genome sequences from animals and humans facilitated an in-depth phylogeographic analysis.

Method
RT-qPCR; genomic sequencing
Sample type
diagnostic material
Geographic raw
Germany, Austria, Switzerland and Liechtenstein
Extraction confidence 0.83
Key finding

Wild shrews were confirmed to carry Borna disease virus 1, consistent with surveillance of the natural reservoir host.

Virus
Host
Location
Supporting text

BoDV-1 infection was confirmed by RT-qPCR in 207 domestic mammals, 28 humans and seven wild shrews.

Method
RT-qPCR
Sample type
diagnostic material
Geographic raw
Germany, Austria, Switzerland and Liechtenstein
1 records
Extraction confidence 0.90
Key finding

BoDV-1 is maintained in the bicolored white-toothed shrew, whose limited mobility shapes the virus’s restricted geographic distribution across parts of Central Europe.

Virus
Location
Supporting text

Borna disease virus 1 (BoDV-1) is the causative agent of Borna disease ... resulting from spill-over infection from its natural reservoir host, the bicolored white-toothed shrew (Crocidura leucodon). ... Consistent with the low mobility of its reservoir host, BoDV-1 sequences showed a remarkable geographic association, with individual phylogenetic clades occupying distinct areas.

Method
phylogeographic analysis; molecular epidemiology; RT-qPCR
Geographic raw
Germany, Austria, Switzerland and Liechtenstein
1 records
Extraction confidence 0.98
Key finding

Human infections with Borna disease virus 1 were caused by spillover from the natural reservoir host, the bicolored white-toothed shrew (Crocidura leucodon).

Virus
Location
Supporting text

Borna disease virus 1 (BoDV-1) ... resulting from spill-over infection from its natural reservoir host, the bicolored white-toothed shrew (Crocidura leucodon). ... BoDV-1 infection was confirmed by RT-qPCR in 207 domestic mammals, 28 humans and seven wild shrews.

Method
RT-qPCR; genome sequencing; phylogeographic analysis
Study design
molecular epidemiology
Transmission direction
animal-to-human
Geographic raw
Germany, Austria, Switzerland and Liechtenstein