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

Arnt Ebinger, Pauline D. Santos, Florian Pfaff, Ralf Dürrwald, Jolanta Kolodziejek, Kore Schlottau, Viktoria Ruf, Friederike Liesche-Starnecker, Armin Ensser, Klaus Korn, Reiner Ulrich, Jenny Fürstenau, Kaspar Matiasek, Florian Hansmann, Torsten Seuberlich, Daniel Nobach, Matthias Müller, Antonie Neubauer-Juric, Marcel Suchowski, Markus Bauswein, Hans-Helmut Niller, Barbara Schmidt, Dennis Tappe, Daniel Cadar, Timo Homeier-Bachmann, Viola C. Haring, Kirsten Pörtner, Christina Frank, Lars Mundhenk, Bernd Hoffmann, Jochen Herms, Wolfgang Baumgärtner, Norbert Nowotny, Jürgen Schlegel, Rainer G. Ulrich, Martin Beer and Dennis Rubbenstroth ()
Additional contact information
Arnt Ebinger: Friedrich-Loeffler-Institut
Pauline D. Santos: Friedrich-Loeffler-Institut
Florian Pfaff: Friedrich-Loeffler-Institut
Ralf Dürrwald: National Reference Centre for Influenza
Jolanta Kolodziejek: University of Veterinary Medicine Vienna
Kore Schlottau: Friedrich-Loeffler-Institut
Viktoria Ruf: Ludwig-Maximilians-Universität München
Friederike Liesche-Starnecker: University of Augsburg
Armin Ensser: Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)
Klaus Korn: Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)
Reiner Ulrich: Leipzig University
Jenny Fürstenau: Freie Universität Berlin
Kaspar Matiasek: Ludwig-Maximilians-Universität München
Florian Hansmann: Leipzig University
Torsten Seuberlich: University of Bern
Daniel Nobach: Justus-Liebig-University Giessen
Matthias Müller: Bavarian Health and Food Safety Authority
Antonie Neubauer-Juric: Bavarian Health and Food Safety Authority
Marcel Suchowski: Leipzig University
Markus Bauswein: Regensburg University Hospital
Hans-Helmut Niller: Regensburg University
Barbara Schmidt: Regensburg University Hospital
Dennis Tappe: Bernhard Nocht-Institute for Tropical Medicine
Daniel Cadar: Bernhard Nocht-Institute for Tropical Medicine
Timo Homeier-Bachmann: Friedrich-Loeffler-Institut
Viola C. Haring: Friedrich-Loeffler-Institut
Kirsten Pörtner: Department of Infectious Disease Epidemiology
Christina Frank: Department of Infectious Disease Epidemiology
Lars Mundhenk: Freie Universität Berlin
Bernd Hoffmann: Friedrich-Loeffler-Institut
Jochen Herms: Ludwig-Maximilians-Universität München
Wolfgang Baumgärtner: University of Veterinary Medicine Hannover
Norbert Nowotny: University of Veterinary Medicine Vienna
Jürgen Schlegel: Technical University Munich
Rainer G. Ulrich: Friedrich-Loeffler-Institut
Martin Beer: Friedrich-Loeffler-Institut
Dennis Rubbenstroth: Friedrich-Loeffler-Institut

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-52192-x

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