A team of researchers from Kyoto University, Osaka Dental University, and Osaka Metropolitan University announced on Apr. 11 that they have uncovered the detailed structure of a crucial protein-RNA complex in Borna disease virus 1 (BoDV-1), a rare but deadly virus in humans.
Borna disease virus 1 is known to cause severe encephalitis, or inflammation of the brain, which is almost always fatal for those who develop the illness. The virus belongs to the order Mononegavirales, which also includes viruses responsible for Ebola, measles, and rabies.
The researchers used cryo-electron microscopy to obtain high-resolution images of BoDV-1 nucleoprotein-RNA complexes. They then performed computational classification to reconstruct different assembly states and used mutational and functional assays to evaluate how changes affected viral RNA synthesis and assembly. Their work resulted in the first detailed structural description of this nucleoprotein-RNA complex within the Bornaviridae family.
The findings revealed that each nucleoprotein subunit binds eight RNA nucleotides—a binding mode different from related viruses—and forms ring-like assemblies with viral RNA located in an inner groove. Notably, mutations that impaired RNA binding disrupted viral RNA synthesis but did not prevent nucleoprotein assemblies from forming without RNA present. The researchers say these results support an incremental model where assembly and RNA engagement are separate but coordinated processes.
This new molecular framework allows for systematic comparison between Bornaviridae structures and those found in other mononegaviruses. It may also help guide future antiviral research targeting these interactions during viral replication.
Looking ahead, the team plans further analysis using complexes derived from infected cells as well as longer segments of RNA. They intend to combine structural studies with biochemical approaches to observe intermediate formation states and compare them with similar viruses.
