FIRST ISOLATES OF INFECTIOUS HUMAN BORNA-DISEASE VIRUS FROM PATIENTS WITH MOOD DISORDERS

Borna disease virus (BDV), an unique type of non-segmented negative-st randed enveloped RNA virus, is known as an animal pathogen that causes behavioral diseases in higher vertebrates. Past studies have found an tibodies to BDV as well as BDV proteins and genomic transcripts in per ipheral blood mononuclear cells (PBMCs) of infected animals and human psychiatric patients. Here, we present the first isolation of infectio us BDV from such patients' PBMCs. Isolation attempts were conducted wi th randomly collected PBMC samples from 33 psychiatric inpatients, by co-cultivation and long-term passaging with a human cell line. BDV iso lates were identified by infectivity, analysis of viral antigens, sequ encing of one viral gene, and successful infection of animals. Three i ndividual isolates could be recovered. They originated from two bipola r patients with acute depression, and one patient with a chronic obses sive-compulsive disorder. Rescue of human BDV required PBMC samples wi th strong viral antigen expression, and at least 11 subcultures per sa mple, 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 infecti on is one of the environmental factors that contributes to recurrent d epressive illnesses in man. These isolates represent the first three d efined strains of the infectious human BDV.