Crystal Structures of Yeast-Produced Enterovirus 71 and Enterovirus 71/Coxsackievirus A16 Chimeric Virus-Like Particles Provide the Structural Basis for Novel Vaccine Design against Hand-Foot-and-Mouth Disease

• DOI: 10.1128/jvi.00422-15
• Publication Date: 2015-04-02T14:57:24Z
• Authors: Ke Lyu; Ya-Ling He; Hao-Yang Li; Rong Chen
• Keywords: Enterovirus 71; Coxsackievirus; Picornavirus; Virus-like particle

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