A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles
文献类型:期刊论文
作者 | Chen, Jinhuan1,2; Zhang, Xiang1,2,5; Cong, Yao1,2; Zhang, Chao3,4; Zhou, Yu5; Shen, Chaoyun5; Huang, Zhong5; Jiang, Wen6 |
刊名 | JOURNAL OF VIROLOGY |
出版日期 | 2018 |
卷号 | 92期号:2页码:e01257-17 |
ISSN号 | 0022-538X |
关键词 | Virus-like Particles Neutralizing Linear Epitopes Human Enterovirus 71 Mouth-disease Synthetic Peptides Atomic-resolution Capsid Protein Atypical Hand Salt Bridges Cryo-em |
DOI | 10.1128/JVI.01257-17 |
文献子类 | Article |
英文摘要 | Coxsackievirus A6 (CVA6) has recently emerged as one of the predominant causative agents of hand, foot, and mouth disease (HFMD). The structure of the CVA6 mature viral particle has not been solved thus far. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 represent a promising CVA6 vaccine candidate. Here, we report the first cryo-electron microscopy (cryo-EM) structure of the CVA6 VLP at 3.0-A resolution. The CVA6 VLP exhibits the characteristic features of enteroviruses but presents an open channel at the 2-fold axis and an empty, collapsed VP1 pocket, which is broadly similar to the structures of the enterovirus 71 (EV71) VLP and coxsackievirus A16 (CVA16) 135S expanded particle, indicating that the CVA6 VLP is in an expanded conformation. Structural comparisons reveal that two common salt bridges within protomers are maintained in the CVA6 VLP and other viruses of the Enterovirus genus, implying that these salt bridges may play a critical role in enteroviral protomer assembly. However, there are apparent structural differences among the CVA6 VLP, EV71 VLP, and CVA16 135S particle in the surface-exposed loops and C termini of subunit proteins, which are often antigenic sites for enteroviruses. By immunological assays, we identified two CVA6-specific linear B-cell epitopes (designated P42 and P59) located at the GH loop and the C-terminal region of VP1, respectively, in agreement with the structure-based prediction of antigenic sites. Our findings elucidate the structural basis and important antigenic sites of the CVA6 VLP as a strong vaccine candidate and also provide insight into enteroviral protomer assembly. IMPORTANCE Coxsackievirus A6 (CVA6) is becoming one of the major pathogens causing hand, foot, and mouth disease (HFMD), leading to significant morbidity and mortality in children and adults. However, no vaccine is currently available to prevent CVA6 infection. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 are a promising CVA6 vaccine candidate. Here, we present a 3.0-A structure of the CVA6 VLP determined by cryo-electron microscopy. The overall architecture of the CVA6 VLP is similar to those of the expanded structures of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), but careful structural comparisons reveal significant differences in the surface-exposed loops and C termini of each capsid protein of these particles. In addition, we identified two CVA6-specific linear B-cell epitopes and mapped them to the GH loop and the C-terminal region of VP1, respectively. Collectively, our findings provide a structural basis and important antigenic information for CVA6 VLP vaccine development. |
电子版国际标准刊号 | 1098-5514 |
WOS研究方向 | Virology |
语种 | 英语 |
WOS记录号 | WOS:000419042000010 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3366] |
专题 | 生化所2018年发文 |
通讯作者 | Cong, Yao |
作者单位 | 1.Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci,Natl Ctr Prot Shangai, CAS Ctr Excellence Mol Cell Sci,State Key Lab Mol, Shanghai, Peoples R China; 2.Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai, Peoples R China; 3.Guangzhou Women & Childrens Med Ctr, Guangzhou Inst Pediat, Joint Ctr Infect & Immun, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China; 4.Chinese Acad Sci, Inst Pasteur Shanghai, Joint Ctr Infect & Immun, Shanghai, Peoples R China; 5.Chinese Acad Sci, Inst Pasteur Shanghai, Vaccine Res Ctr, CAS Key Lab Mol Virol & Immunol, Shanghai, Peoples R China; 6.Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA |
推荐引用方式 GB/T 7714 | Chen, Jinhuan,Zhang, Xiang,Cong, Yao,et al. A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles[J]. JOURNAL OF VIROLOGY,2018,92(2):e01257-17. |
APA | Chen, Jinhuan.,Zhang, Xiang.,Cong, Yao.,Zhang, Chao.,Zhou, Yu.,...&Jiang, Wen.(2018).A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles.JOURNAL OF VIROLOGY,92(2),e01257-17. |
MLA | Chen, Jinhuan,et al."A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles".JOURNAL OF VIROLOGY 92.2(2018):e01257-17. |
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