OmniVira

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].
PMID39256401 DOI10.1038/s41467-024-52192-x Year2024 Journal Nature communications Nat Commun Languageeng Statusepublish

Abstract

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.

Supporting text Virus Host Location
Borna Disease 4 Borna disease virus 4 Molecular Epidemiology 21 Phylogeny 805 Phylogeography 30 Shrews 15 Adult 71 Animals 1948 Austria 3 Disease Reservoirs 149 Female 289 Genome, Viral 317 Germany 20 Humans 1440 Male 224 Middle Aged 60 Switzerland 9 Zoonoses 397

Evidence records

4 total
Zoonotic Surveillance
2 records · 2 evidence types
Evidence type Viral Detection
1 records
OVE8392 Viral Detection
Key finding

Borna disease virus 1 infection was confirmed by RT-qPCR in 207 domestic mammals, 28 humans, and seven wild shrews within the known endemic parts of Germany, Austria, Switzerland, and Liechtenstein.

Virus
Borna disease virus 1
Host
mammals Mammalia Natural host human Homo sapiens Natural host shrews Soricidae Natural host
Location
Germany Austria Switzerland Liechtenstein
Supporting text

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. 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 | clinical specimens | encephalitis samples
Geographic raw
Germany | Austria | Switzerland | Liechtenstein
Country inferred
DEU | AUT | CHE | LIE
Evidence type Reservoir Ecology
1 records
OVE8393 Reservoir Ecology
Key finding

Borna disease virus 1 spill‑over infections originate from its natural reservoir, the bicolored white‑toothed shrew (Crocidura leucodon), and circulation is restricted to parts of central Europe.

Virus
Borna disease virus 1
Host
bicolored shrew Crocidura leucodon Natural host
Location
Germany Austria Switzerland Liechtenstein
Supporting text

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.

Method
RT‑qPCR detection | phylogeographic analysis
Sample type
diagnostic material from suspected BoDV‑1‑induced encephalitis cases | wild shrews
Geographic raw
parts of Germany | Austria | Switzerland | Liechtenstein
Country inferred
AUT | CHE | LIE
Transmission Evidence
1 records · 1 evidence types
Evidence type Spillover Event
1 records
OVE8395 Spillover Event
Key finding

Human infections with Borna disease virus 1 appear to result from local spill-over transmission from the bicolored white-toothed shrew reservoir within about 40 km of patients’ home regions.

Virus
Borna disease virus 1
Host
human Homo sapiens Natural host bicolored shrew Crocidura leucodon Natural host
Location
patient´s home region
Supporting text

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 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.

Method
whole-genome sequencing | phylogeographic analysis | genetic distance comparison
Study design
molecular epidemiology and phylogeographic analysis of human and animal BoDV-1 sequences
Transmission direction
animal-to-human
Geographic raw
patient´s home region
Genomic Evolution
1 records · 1 evidence types
Evidence type Phylogenetic Evolution
1 records
OVE8394 Phylogenetic Evolution
Key finding

Phylogeographic and phylogenetic analyses of 136 new Borna disease virus 1 genomes from animals and humans revealed distinct geographic clades occupying restricted endemic areas in Central Europe.

Virus
Borna disease virus 1
Host
animals Metazoa Context pending human Homo sapiens Natural host
Location
Not specified
Supporting text

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

Genes or proteins
genome
Analysis methods
phylogeographic analysis | phylogenetic analysis