Nucleocytoplasmic Shuttling of Viral Proteins in Borna Disease Virus Infection

Nuclear import and export of viral RNA and proteins are critical to the replication cycle of viruses that replicate in the nucleus. Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that belongs to the order Mononegavirales. BDV has several distinguishing features, one of the most striking being the site of its replication. BDV RNA is transcribed and replicated in the nucleus, while most other negative-strand RNA viruses replicate in the cytoplasm. Therefore, the nucleocytoplasmic trafficking of BDV macromolecules plays a key role in virus replication. Growing evidence indicates that several BDV proteins, including the nucleoprotein, phosphoprotein, protein X and large protein, contribute to the nucleocytoplasmic trafficking of BDV ribonucleoprotein (RNP). The directional control of BDV RNP trafficking is likely determined by the ratios of and interactions between the nuclear localization signals and nuclear export signals in the RNP. In this review, we present a comprehensive view of several unique mechanisms that BDV has developed to control its RNP trafficking and discuss the significance of BDV RNP trafficking in the replication cycle of BDV.