Bluetongue virus structure and assembly

•BTV as a model complex, non-enveloped dsRNA virus.•Each stage of BTV replication defined, some by novel techniques.•Unexpected similarities in entry mechanisms between capsid and enveloped viruses.•Infectious virus assembly achieved in a cell-free reconstitution system.•RNA genome packaging is ordered and is disreputable.

Bluetongue virus (BTV) is an insect-vectored emerging pathogen of wild ruminants and livestock in many parts of the world. The virion particle is a complex structure of consecutive layers of protein surrounding a genome of ten double-stranded (ds) RNA segments. BTV has been studied as a model system for large, non-enveloped dsRNA viruses. Several new techniques have been applied to define the virus-encoded enzymes required for RNA replication to provide an order for the assembly of the capsid shell and the protein sequestration required for it. Further, a reconstituted in vitro system has defined the individual steps of the assembly and packaging of the genomic RNA. These findings illuminate BTV assembly and indicate the pathways that related viruses might use to provide an informed starting point for intervention or prevention.