In 1985, Rott and Koprowski reported that serum from patients with bipolar disorder reacted with cells infected with Borna disease virus (BDV)1,an unclassified infectious agent named after a town in Saxony (Eastern Germany) where an outbreak of equine encephalitis

In 1985, Rott and Koprowski reported that serum from patients with bipolar disorder reacted with cells infected with Borna disease virus (BDV)1,an unclassified infectious agent named after a town in Saxony (Eastern Germany) where an outbreak of equine encephalitis in the late 1800s crippled the Prussian cavalry2. Intrigued by the notion that an infectious agent might be implicated in human neuropsychiatric disease, we and others began to pursue the characterization of this elusive neurotropic virus. BDV nucleic acids were isolated by subtractive hybridization in the late 1980s, the first successful application of subtractive cloning in pathogen discovery3,4.Over the next five years, the genome was cloned, and the virus was visualized and classified as the prototype of a new genus of nonsegmented negative-strand (NNS) RNA virus with unusual properties: nuclear replication and transcription, posttranscriptional modification of selected mRNA species by splicing, low level productivity, a broad host range, neurotropism and the capacity for persistence5. It was widely thought, and proposed in a review in this journal in 1995, that the introduction of specific reagents such as recombinant proteins and nucleic acid probes would allow rapid assessment of the role of BDV in human disease6. How have we fared? A recent publication by Fukuda and colleagues provides a context within which to review our knowledge of BDV epidemiology7.