Structural and Biophysical Characterization of the Borna Disease Virus-1 Phosphoprotein

The mammalian orthobornavirus-1 commonly referred as Borna disease virus-1 (BoDV-1), is the prototype member of the Bornaviridae family associated with neurological impairments, encephalitis, and death in horses, cattle, and humans. Determining the structural organization of viral replication complexes and unraveilling the impact of infection on cellular homeostasis represent important challenges in virology.  As with other single stranded non-segmented RNA viruses, the BoDV-1 encodes a viral phosphoprotein (P) that binds both the viral polymerase (L) and nucleoprotein (N), and acts as a molecular chaperone required for the formation of functional replication/transcription complex. In this study, size-exclusion chromatography coupled with multi-angle laser X-ray scattering, circular dichroism, and differential scanning calorimetry were employed to determine the structural and biophysical organization of the BoDV-1 P. The protein was shown to adopts a stable tetrameric structure, with the regions outside the oligomerization domain being highly flexible. The long coiled helical structure splits into two parts at the midpoint of the oligomerization domain by a helix-breaking motif, which appears to be highly conserved across the members of the Bornaviridae. The stable tetramerization nature of the BoDV-1 P enables the viral protein to protect the viral RNA genome from host endonucleases, and effectively binds to the other components of the replicase complex.
(BNU)