Meet a researcher uncovering how viruses replicate in unexpected places
A virus that can invade the brain and cause fatal neurological disease has long puzzled scientists because it replicates in a place most viruses avoid: the nucleus of infected cells.
For Eric Gibbs, a postdoctoral researcher in the Department of Pharmacology at the School of Medicine, that mystery became an unexpected entry point into a new area of research.
Borna disease virus 1 (BoDV-1) is unusual among RNA viruses because it replicates inside the nucleus rather than the cytoplasm, a strategy whose mechanism has remained unknown. As a co-first author on a study published in Nucleic Acids Research, Gibbs contributed to uncovering how this process works at the molecular level, helping answer a longstanding question in virology.
This groundbreaking research, led by the Chakrapani Lab at Case Western Reserve University in collaboration with researchers at the University of Toledo and Kyoto University, captured the first detailed 3D structure of the virus’s RNA polymerase complex. The image details the molecular machinery responsible for copying viral genetic material and producing the proteins needed for infection and spread. Using advanced cryo–electron microscopy (cryo-EM), the team resolved the structure at near-atomic resolution, revealing how the polymerase is assembled and how it interacts with a key phosphoprotein cofactor to initiate transcription. Their findings also identified specific structural regions that are essential for efficient viral gene expression, providing a direct link between the enzyme’s architecture and its function. The study further uncovered subtle but critical features within the polymerase, including flexible structural elements that appear to guide the initiation of RNA synthesis. Together, these insights could lead to uncovering how BoDV-1 replicates within the nucleus and connect it to broader patterns seen across other negative-strand RNA viruses.
For Gibbs, stepping into this work represented both a scientific and personal expansion.
“Viral replication is not a subject I had previously studied, but the training and cryo-EM resources at CWRU allowed me to make significant contributions to this field,” he said. “This not only led to high impact research, but also expanded my personal knowledge and interests, which will lead to further meaningful research.”
That experience underscores the role of CWRU’s structural biology infrastructure in enabling high-impact, collaborative discovery. Access to cryo-EM resources at the Cleveland Center for Membrane and Structural Biology made it possible for researchers across institutions to visualize the viral machinery in unprecedented detail. Although BoDV-1 primarily affects livestock, it has been linked to rare but severe neurological disease in humans, including encephalitis. By revealing how the virus replicates at the molecular level, the study provides a foundation for future efforts to develop targeted antiviral strategies.
Looking ahead, Gibbs and his collaborators plan to investigate how multiple polymerase complexes assemble into larger functional units and how the virus interacts with host proteins inside the nucleus by continuing to explore a system that challenges the conventional understandings of viral replication.
