Molecular biology of Borna disease virus and persistence

Borna disease virus (BDV) causes central nervous system (CNS) disease that is frequently manifested by behavioral abnormalities. Recent evidence indicates that the natural host range and geographic distribution of BDV is wider than originally thought BDV has been molecularly characterized as a non-segmented, negative single-stranded (NNS) RNA virus. Its genome (ca 8.9 kb), the smallest among known NNS RNA viruses, has an organization similar to that of other members of the order Mononegavirales. BDV has the property, unique among known animal NNS RNA viruses, of a nuclear site for the replication and transcription of its genome. The nucleocytoplasmic transport of BDV macromolecules is an essential component of the life cycle of BDV. An overlap of transcription units and transcriptive signals, overlap of ORFs, transcriptional readthrough and RNA splicing regulate expression of the BDV compact genome. The concurrent use of such diversity of strategies for the regulation of virus gene expression is unique among known NNS RNA viruses. Moreover, BDV appears to have also an unusual assembly process. Based on its unique genetic and biological features, BDV is considered to be the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales. Therefore, the investigation of the molecular biology of BDV may provide new insights about the biology of mononegaviruses, which include important human pathogens.