Crystal structures of EV71 recombinant virus particles provide insights into vaccine design [Molecular Biophysics]

December 9th, 2014 by Lyu, K., Wang, G.-C., He, Y.-L., Han, J.-F., Ye, Q., Qin, C.-F., Chen, R.

Hand-foot-and-mouth disease (HFMD) remains a major health concern in the Asia-Pacific regions and its major causative agents include human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). A desirable vaccine against HFMD is supposed to be multivalent and able to elicit protective responses against multiple HFMD causative agents. Previously, we have demonstrated that a thermo-stable recombinant EV71 vaccine candidate can be produced by the insertion of a foreign peptide into the BC loop of VP1 without affecting viral replication. Here we present crystal structures of two different naturally occurring empty particles, one from a clinical C4 strain EV71 and the other from its recombinant virus containing an insertion in the VP1 BC loop. Crystal structure analysis demonstrated that the inserted foreign peptide is well exposed on the particle surface without significant structural changes in the capsid. Importantly, such insertions do not seem to affect the virus uncoating process, as illustrated by the conformational similarity between an uncoating intermediate of another recombinant virus and that of EV71. Especially, at least 18 residues from N-terminus of VP1 are transiently externalized. Together, our study provided insights into vaccine development against HFMD.