Zika: Characterisation of Zika virus neutralisation and virion structure by cryogenic electron microscopy and 3D reconstruction.

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Cryogenic electron microscopy (CryoEM) has the potential to determine close-to atomic
resolution structures for macromolecular assemblies and in particular icosahedral viruses.
Such structures provide insights into mechanisms of virus assembly, maturation and entry.
Mechanistic studies of antibody neutralisation are also informed by structure analysis of
viruses decorated with Monoclonal antibody fragments (MAbs).
Zika virus (ZIKV), being a member of the Flaviviridae is expected to exhibit an icosahedral
virion structure similar to that of dengue virus (DENV), in which heterotetramers of E-M-M-E
coat the outer surface of the virion (1). An atomic model of the mature virion exterior,
determined by cryoEM at 2-4 angstroms resolution would be a considerable asset to
researchers working towards the production of an effective vaccine. Recent studies of DENV2
virions decorated with a neutralising monoclonal antibody revealed that the bound antibody
locks E dimers together, preventing the rearrangement necessary to expose the fusion
peptide and allow entry (2).
We propose to calculate an atomic resolution model of the ZIV particle alone and bound to
both broadly-reactive anti-flavivirus MAbs and specific MAbs directed at ZIV. This study has
the potential to inform both vaccine design and development of improved diagnostics.