The dynamics of cell entry and genome replication in a model complex virus

Bluetongue virus (BTV), a complex non-enveloped virus with a genome of ten double-stranded RNA segments, is an important pathogen and model for many similar large non-enveloped viruses (including the medically important rotaviruses).

Previous studies have provided a well-understood replication cycle, a large range of research reagents and many novel assay systems, all complemented by high resolution atomic structures of many viral proteins.

Notably, the recent structure of the viral polymerase in situ, a critical point of replication, has provided a unique opportunity to investigate many details involved in the virus life cycle.

To achieve this we will will use state-of-the-art techniques such as cryoEM, cryo-ET, FCS and FRET in addition to our established in vitro and in vivo assays to determine how BTV entry to the cell causes the polymerase to initiate genome transcription from the 10 genomic dsRNAs and how this process differs from the later process of genome replication which follows the packaging of RNA during assembly.

We will define how these processes link to the maturation of newly assembled virus particles and their exit from the cell.

Our findings will have the potential to develop laboratory data to translational applications in future design of antiviral and vaccines.