Meta-analysis of putative human bornavirus sequences fails to provide evidence implicating Borna disease virus in mental illness

All Borna disease virus (BDV) sequences derived from human specimens published till date were thoroughly analysed and compared to sequences of BDV laboratory strains and to BDV sequences from animals which succumbed to classical Borna disease (BD). Despite high sequence conservation of the BDV genome, animal-derived BDV sequences clustered according to their geographic origin. However, in marked contrast, human-derived BDV sequences did not cluster according to their geographic origin but showed high sequence identities to BDV laboratory strains and animal-derived BDVs handled in the laboratories reporting the human strains. Japanese, US, Australian and French human-derived BDV sequences proved to be identical or very similar to animal-derived BDV sequences from Germany, although the human specimens were collected hundreds to thousands of miles away from the central European BD endemic regions. These findings suggest that previous studies linking BDV to human neuropsychiatric disease may have been compromised by inadvertent sample contamination.