Synthetic Virus-like Particles and How to Make Them in Plants

Viral capsids play an essential role in the replication cycle of viruses. Not only do they protect the labile genetic material from degradation but they play a vital role in the transmission of infections both within and between host organisms. This occurs through interactions with cellular components, such as receptors, and, in many cases, with the vectors responsible for virus transmission. Furthermore, it is usually the capsid protein to which a host initially reacts when mounting a defence response, be it through adaptive or innate immunity. For this reason many vaccines are based either on inactivated virus particles or on recombinant virus-like particles (VLPs); the ability of viral capsids to elicit an immune response is also exploited to produce antibody-based diagnostic reagents. VLPs have also been exploited in bionanotechnology for such purposes as bioimaging and drug delivery.
Given the importance of viral capsids in so many contexts, there has been huge interest in understanding their detailed atomic structures. Such studies have historically depended on isolating the virus of interest, finding a means of propagating it safely and efficiently in at least milligram quantities followed crystallisation and structure determination X-ray crystallography. This is a laborious process which, for many economically significant viruses, has not proved possible. However, recent developments in next-generation sequencing, bioinformatics, plant-based transient expression and cryo-electron microscopy make it possible to produce a virus capsid and determine its structure without ever needing to propagate the parent virus. To demonstrate the feasibility of this approach we have expressed the coat proteins of several viruses of both plants and animals, in plants, isolated the VLPs and determined their structures by cryo-EM. Furthermore, we have used the VLPs to develop novel diagnostic reagents and candidate vaccines.