First isolates of infectious human Borna disease virus from patients with mood disorders

Borna disease virus (BDV), an unique type of non-segmented negative-stranded enveloped RNA virus, is known as an animal pathogen that causes behavioral diseases in higher vertebrates. Past studies have found antibodies to BDV as well as BDV proteins and genomic transcripts in peripheral blood mononuclear cells (PBMCs) of infected animals and human psychiatric patients. Here, we present the first isolation of infectious BDV from such patients' PBMCs. Isolation attempts were conducted with randomly collected PBMC samples from 33 psychiatric inpatients, by co-cultivation and long-term passaging with a human cell line. BDV isolates were identified by infectivity, analysis of viral antigens, sequencing of one viral gene, and successful infection of animals. Three individual isolates could be recovered. They originated from two bipolar patients with acute depression, and one patient with a chronic obsessive-compulsive disorder. Rescue of human BDV required PBMC samples with strong viral antigen expression, and at least 11 subcultures per sample. Genetic and biological properties point to a close relationship of human and animal strains, but also to the uniqueness of each human isolate. Isolation of BDV from patients with major mood disorders at a time of acute depression strengthens the possibility that BDV infection is one of the environmental factors that contributes to recurrent depressive illnesses in man. These isolates represent the first three defined strains of the infectious human BDV.