Comprehensive phylogeographic analysis of zoonotic Borna disease virus 1 (BoDV-1) infections in domestic mammals and humans

Borna disease virus 1 (BoDV-1) causes fatal encephalomyelitis in domestic mammals and humans following spill-over transmission from shrews of the genus Crocidura, the known natural reservoir host. The known endemic areas of BoDV-1 are restricted to parts of Germany, Austria, Switzerland and Liechtenstein, whereas specific transmission routes remain obscure. In this study, we performed a comprehensive phylogeographic analysis of BoDV-1 to assess potential sources of human BoDV-1 infections. We collected material and metadata of 182 domestic mammals, 21 human patients, and seven shrews with confirmed BoDV-1 infection from Germany and Switzerland. Complete or partial BoDV-1 genome sequences were generated from 90 domestic mammals, 18 humans and all seven shrews and analysed together with 128 previously published BoDV-1 sequences. Most cases originated from the previously known endemic areas with few exceptions, some of which may indicate previously unknown risk areas for BoDV-1 transmission. In line with the strongly territorial reservoir host, the sequences showed a remarkable geographic association with distinct phylogenetic clades occupying barely overlapping dispersal areas. Our work raised the number of confirmed human BoDV-1 infections to 41. The closest genetic relatives of most available human BoDV-1 sequences were located at distances below 50 km (median 22 km), indicating that the majority of zoonotic spill-over transmissions occurs close to the patient´s residence.