Trafficking of viral genomic RNA into and out of the nucleus: influenza, Thogoto and Borna disease viruses

Most RNA viruses that lack a DNA phase replicate in the cytoplasm. However, several negative-stranded RNA viruses such as influenza, Thogoto, and Borna disease viruses replicate their RNAs in the nucleus, taking advantage of the host cellʹs nuclear machinery. A challenge faced by these viruses is the trafficking of viral components into and out of the nucleus through the nuclear membrane. The genomic RNAs of these viruses associate with proteins to form large complexes called viral ribonucleoproteins (vRNPs), which exceed the size limit for passive diffusion through the nuclear pore complex (NPC). To insure efficient transport across the nuclear membrane, these viruses use nuclear import and export signals exposed on the vRNPs. These signals recruit the cellular import and export complexes, which are responsible for the translocation of the vRNPs through the NPC. The ability to control the direction of vRNP trafficking throughout the viral life cycle is critical. Various mechanisms, ranging from simple post-translational modification to complex, sequential masking-and-exposure of localization signals, are used to insure the proper movement of the vRNPs.