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Publication Abstract from PubMed

Human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two major causative agents for hand-foot-and-mouth diseases (HFMD). Previously we demonstrated that a virus-like particle (VLP) for EV71 produced from Saccharomyces cerevisiae is a potential vaccine candidate against EV71 infection, and an EV71/CVA16 chimeric VLP can elicit protective immune response against both virus infections. Here we presented the crystal structures of both VLPs, showing that both the linear and conformational neutralization epitopes identified in EV71 are mostly preserved on both VLPs. The substitution of only 4 residues in the VP1 GH loop converted strongly negative charged surface patches formed by portions of the SP70 epitope in EV71 VLP into a relatively neutral surface in the chimeric VLP, which likely accounted for the additional neutralization capability of the chimeric VLP against CVA16 infection. Such local variations in the amino acid sequences and the surface charge potential are also present in different types of polioviruses. In comparison to EV71 VLP, the chimeric VLP exhibits structural changes at the local site of amino acid replacement and the surface loops of all capsid proteins. This is consistent with the observation that the VP1 GH loop located near the pseudo 3-fold junction is involved in extensive interactions with other capsid regions. Furthermore, portions of VP0 and VP1 in EV71 VLP are at least transiently exposed, revealing the structural flexibility of the VLP. Together, our structural analysis provided insights into the structural basis of enterovirus neutralization and novel vaccine design against HFMD and other enterovirus-associated diseases. IMPORTANCE: Our previous studies demonstrated that the EV71 VLP produced from yeast is a vaccine candidate against EV71 infection and a chimeric EV71/CVA16 VLP with the substitution of 4 amino acids in the VP1 GH loop can confer protection against both EV71 and CVA16 infections. This study reported the crystal structures of both the EV71 VLP and the chimeric EV71/CVA16 VLP, and revealed that the major neutralization epitopes of EV71 are mostly preserved in both VLPs. In addition, the mutated VP1 GH loop in the chimeric VLP is well exposed on the particle surface and exhibits different surface charge potential from that contributed by the original VP1 GH loop in EV71 VLP. Together, this study provided insights into the structural basis of enterovirus neutralization and evidence that the yeast-produced VLPs can be developed into novel vaccines against HFMD and other enterovirus-associated diseases.

Crystal structures of yeast-produced enterovirus 71 and enterovirus 71/coxsackievirus A16 chimeric virus-like particles provide structural basis for novel vaccine design against hand-foot-and-mouth disease.,Lyu K, He YL, Li HY, Chen R J Virol. 2015 Apr 1. pii: JVI.00422-15. PMID:25833050^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.