Borna disease virus 1 (BoDV-1) is a neurologic disease of horses and sheep that causes rare human infections. The outcome in those who develop disease almost always results in inflammation in the brain or fatal encephalitis.
The nucleoprotein–RNA complex in viruses protects the RNA genome and supports viral RNA synthesis. Increasing our understanding of the structure of this complex is essential to targeting viral replication. Structural characterization has been completed for several viruses in the same order as BoDV-1 (Mononegavirus) that more commonly infect humans, but detailed information for the family Bornaviridae has not been sufficiently explored.
“Bornaviruses are less well known than many other human RNA viruses, yet they represent the last major unresolved case for nucleoprotein–RNA structural analysis among human-infecting mononegaviruses,” says Yukihiko Sugita, PhD, associate professor at Kyoto University. “Closing this long-standing gap and connecting structural biology with virological function were major motivations for our team.”
Using cryo-electron microscopy, researchers from Kyoto University, Osaka Dental University, and Osaka Metropolitan University obtained high-resolution images of BoDV-1 nucleoprotein–RNA complexes and performed computational classification to separate and reconstruct the distinct assembly states of each complex in the sample. They also used mutational and functional assays to test nucleoprotein–RNA residues and evaluate their roles in viral RNA synthesis and assembly.
This work is published in Science Advances in the paper, “Structure and assembly of Borna disease virus 1 nucleoprotein-RNA complexes.”
These findings are the first detailed structural description of the nucleoprotein–RNA complex in the family Bornaviridae and revealed the three-dimensional structure of this nucleoprotein-RNA complex, showing ring-like assemblies and viral RNA binds in the inner groove. The researchers also found that each nucleoprotein subunit accommodates eight RNA nucleotides, suggesting a binding mode distinct from those reported for other related viruses.
The work also reveals that mutations impairing RNA binding disrupt viral RNA synthesis, but that nucleoprotein assemblies can form even without RNA. Together, these findings suggest an incremental model in which nucleoprotein assembly and RNA engagement are separate but coordinated processes.
This study provides a molecular framework for a systematic comparison of Bornaviridae nucleoprotein–RNA architecture alongside that of other mononegaviruses, and supports broader questions about the principles governing nucleoprotein–RNA interactions. It also lays the groundwork for future antiviral studies targeting viral replication through nucleoprotein–RNA interactions.
Next, the team would like to analyze complexes derived from infected cells as well as those with longer RNA segments. They also plan to integrate structural analysis and biochemical approaches in order to observe intermediate complex formation states and compare them with those of related viruses.
