Borna Disease Virus Infection of Adult and Neonatal Rats: Models for Neuropsychiatric Disease

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Borna disease virus (BDV) is a newly classified RNA virus (Briese et al. 1994; Cubitt et al. 1994; Schneemann et al. 1995), worldwide in distribution, that infects the central nervous system (CNS) of warm-blooded animals to cause behavioral disturbances reminiscent of autism, schizophrenia, and mood disorders (Lipkin et al. 1995). It is not lytic in vitro or in vivo, replicates at lower levels than most known viruses and is dissimilar in nucleic acid and protein sequence to other infectious agents (de la Torre 1994; Schneemann et al. 1995). Thus, BDV eluded characterization until its nucleic acids were cloned by subtractive hybridization (Lipkin et al. 1990; VandeWoude et al. 1990). The molecular biology of BDV is unusual in many respects, including a nuclear localization for replication and transcription, overlap of open reading frames (ORFs) and transcription units, post-transcriptional modification of subgenomic RNAs, and marked conservation of coding sequence across a wide variety of animal species and tissue culture systems. These features led to its recent recognition by the International Committee on Taxonomy of Viruses as the prototype of a new family, Bornaviridae, within the nonsegmented negative-strand RNA viruses (de la Torre 1994; Schneemann et al. 1995). Natural infection has been confirmed in horses, sheep, cattle, birds and cats. Primates can be infected experimentally (Stitz et al. 1980) and recent reports suggest an increased prevalence of BDV infection in mood disorders and schizophrenia (Amsterdam et al. 1985; Bode et al. 1988, 1992, 1993; Fu et al. 1993; Kishi et al. 1995; Waltrip II et al. 1995).