Structural studies of the calcivirus entry pathway – conformational flexibility as a marker of virulence?

David Bhella, MRC - University of Glasgow Centre for Virus Research

Lee Sherry, Charlotte Lewis, Margaret Hosie MRC – University of Glasgow Centre for Virus Research, UK

Structure & Pathogenesis

Structural studies of caliciviruses have shown that, for all viruses studied to date, native virions assemble as T=3 icosahedral capsids with pronounced dimeric spikes on their outer surfaces. These spikes comprise dimers of the P-domain of the major capsid protein. The pose of the P-dimers has however varied between ‘raised’ and ‘resting’ forms. Further, these spikes are often found to be mobile – leading to blurring of density on cryo-EM reconstructions. We previously showed that P-domain mobility was a feature of the feline calicivirus capsid, following receptor engagement. This was accompanied by assembly of a portal-like assembly, consisting of 12 copies of the minor capsid protein VP2 – that is critical for delivery of the viral genome across the endosomal membrane.

We have extended our study to explore the structure of virus-receptor complexes for clinical isolates of feline calicivirus associated with mild respiratory disease and with virulent systemic disease. We have found striking differences in capsid flexibility and hypothesise that entry pathway may be a factor in the propensity of a calicivirus to cause mild or severe disease.