Insights into the Evolution of a Complex Virus from the Crystal Structure of Vaccinia Virus D13

The morphogenesis of poxviruses such as vaccinia virus (VACV) sees the virion shape mature from spherical to brick-shaped. Trimeric capsomers of the VACV D13 protein form a transitory, stabilizing lattice on the surface of the initial spherical immature virus particle. The crystal structure of D13 reveals that this major scaffolding protein comprises a double β barrel “jelly-roll” subunit arranged as pseudo-hexagonal trimers. These structural features are characteristic of the major capsid proteins of a lineage of large icosahedral double-stranded DNA viruses including human adenovirus and the bacteriophages PRD1 and PM2. Structure-based phylogenetic analysis confirms that VACV belongs to this lineage, suggesting that (analogously to higher organism embryogenesis) early poxvirus morphogenesis reflects their evolution from a lineage of viruses sharing a common icosahedral ancestor. ► Poxvirus D13 acts as a scaffold for the morphogenesis of spherical immature virions ► D13 has a double “jelly-roll” structure, like other large DNA virus capsid proteins ► Structure-based phylogenetics places D13 into an icosahedral viral lineage ► Poxvirus morphogenesis reflects Vaccinia virus evolution from an icosahedral ancestor