Negative-sense RNA viruses are a very large family that play an important role in human and animal health. Members include important human and animal pathogens such as rabies virus, measles virus, Ebola virus, and bornaviruses. These viruses share a conserved genome organization, with their RNA genomes encapsidated by viral nucleoprotein, which serves as a template for an RNA-dependent RNA polymerase (L protein) that performs both transcription of viral mRNAs and replication of the genome. Despite this conserved genome structure, the replication strategies are quite diverse. This project will focus on members of the nuclear-replicating viruses called bornaviruses.
Bornaviruses perform replication and transcription in the nucleus of an infected cell. Bornaviruses are found to infect many animal species, with rare transmission to humans. Inside the nucleus, they cause a persistent infection which can last many years before reactivation. Recently, the Keown lab has become interested in the viral machinery that performs the processes of replication and transcription (see Carrique et al., Nature Communications, 2025). In this project, we will expand our previous work to understand how these viruses perform these processes inside infected cells.
This project will make extensive use of the structural biology techniques of single-particle cryo-EM and cryo-electron tomography. We will seek to understand how viral complexes assemble under both in vitro and in vivo conditions.
