Journal: J Virol / Year: 2014 Title: Cryo-electron microscopy study of insect cell-expressed enterovirus 71 and coxsackievirus a16 virus-like particles provides a structural basis for vaccine development. Authors: Minqing Gong / Hongtao Zhu / Jun Zhou / Chunting Yang / Jing Feng / Xiaojun Huang / Gang Ji / Honglin Xu / Ping Zhu / Abstract: Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two most common etiological agents responsible for the epidemics of hand, foot, and mouth disease (HFMD), a childhood illness with ...Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two most common etiological agents responsible for the epidemics of hand, foot, and mouth disease (HFMD), a childhood illness with occasional severe neurological complications. A number of vaccine candidates against EV71 or CA16 have been reported; however, no vaccine is currently available for clinical use. Here, we generated a secreted version of EV71 and CA16 virus-like particles (VLPs) using a baculovirus-insect cell expression system and reconstructed the three-dimensional (3D) structures of both VLPs by cryo-electron microscopy (cryo-EM) single-particle analysis at 5.2-Å and 5.5-Å resolutions, respectively. The reconstruction results showed that the cryo-EM structures of EV71 and CA16 VLPs highly resemble the recently published crystal structures for EV71 natural empty particles and CA16 135S-like expanded particles, respectively. Our cryo-EM analysis also revealed that the majority of previously identified linear neutralizing epitopes are well preserved on the surface of EV71 and CA16 VLPs. In addition, both VLPs were able to induce efficiently neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71- and CA16-associated HFMD. IMPORTANCE: The recent outbreaks of hand, foot, and mouth disease (HFMD) in the Asia Pacific region spurred the search for effective vaccines against EV71 and CA16 viruses, the two most common ...IMPORTANCE: The recent outbreaks of hand, foot, and mouth disease (HFMD) in the Asia Pacific region spurred the search for effective vaccines against EV71 and CA16 viruses, the two most common etiological agents responsible for HFMD. In this paper, we show that secreted versions of EV71 and CA16 VLPs generated in the baculovirus-insect cell expression system highly resemble the crystal structures of their viral conterparts and that the majority of previously identified linear neutralizing epitopes are well preserved on the VLP surfaces. In addition, the generated VLPs can efficiently induce neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71- and CA16-associated HFMD.
History
Deposition
Mar 12, 2014
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Header (metadata) release
Apr 16, 2014
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Map release
Apr 16, 2014
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Update
May 14, 2014
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Current status
May 14, 2014
Processing site: PDBe / Status: Released
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Structure visualization
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Surface view with section colored by density value
Category: CCD / Film or detector model: GATAN ULTRASCAN 4000 (4k x 4k)
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Model: Titan Krios / Image courtesy: FEI Company
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Image processing
Final reconstruction
Applied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 5.5 Å / Resolution method: OTHER / Number images used: 21403
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Human coxsackievirus A16
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http://ftp.pdbj.org/pub/emdb/structures/EMD-2608
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