Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody.
Longfa Xu,Qingbing Zheng,Shaowei Li,Maozhou He,Yangtao Wu,Yongchao Li,Rui Zhu,Hai Yu,Qiyang Hong,Jie Jiang,Zizhen Li,Shuxuan Li,Huan Zhao,Lisheng Yang,Wangheng Hou,Wei Wang,Xiangzhong Ye,Jun Zhang,Timothy S. Baker,Tong Cheng,Z. Hong Zhou,Z. Hong Zhou,Xiaodong Yan,Xiaodong Yan,Ningshao Xia +24 more
TLDR
The isolation of two forms of stable CVA6 particles-procapsid and A-particle-with excellent biochemical stability and natural antigenicity to serve as vaccine candidates are demonstrated and an immune-dominant neutralizing epitope is identified which can be exploited for vaccine development.Abstract:
Coxsackievirus A6 (CVA6) has recently emerged as a major cause of hand, foot and mouth disease in children worldwide but no vaccine is available against CVA6 infections. Here, we demonstrate the isolation of two forms of stable CVA6 particles-procapsid and A-particle-with excellent biochemical stability and natural antigenicity to serve as vaccine candidates. Despite the presence (in A-particle) or absence (in procapsid) of capsid-RNA interactions, the two CVA6 particles have essentially identical atomic capsid structures resembling the uncoating intermediates of other enteroviruses. Our near-atomic resolution structure of CVA6 A-particle complexed with a neutralizing antibody maps an immune-dominant neutralizing epitope to the surface loops of VP1. The structure-guided cell-based inhibition studies further demonstrate that these loops could serve as excellent targets for designing anti-CVA6 vaccines. Coxsackievirus A6 (CVA6) causes hand, foot and mouth disease in children. Here the authors present the CVA6 procapsid and A-particle cryo-EM structures and identify an immune-dominant neutralizing epitope, which can be exploited for vaccine development.read more
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Journal ArticleDOI
Emerging Coxsackievirus A6 Causing Hand, Foot and Mouth Disease, Vietnam.
Nguyen To Anh,Le Nguyen Truc Nhu,Hoang Minh Tu Van,Nguyen Thi Thu Hong,Tran Tan Thanh,Vu Thi Ty Hang,Nguyen Thi Han Ny,Lam Anh Nguyet,Tran Thi Lan Phuong,Le Nguyen Thanh Nhan,Nguyen Thanh Hung,Truong Huu Khanh,Ha Manh Tuan,Ho Lu Viet,Nguyen Tran Nam,Do Chau Viet,Phan Tu Qui,Bridget Wills,Sarawathy Sabanathan,Nguyen Van Vinh Chau,Louise Thwaites,H. Rogier van Doorn,Guy E. Thwaites,Maia A. Rabaa,Le Van Tan +24 more
TL;DR: The data show that CV-A6 is an emerging pathogen and emphasize the necessity of active surveillance and understanding the mechanisms that shape the pathogen evolution and emergence, which is essential for development and implementation of intervention strategies.
Journal ArticleDOI
Recent development of enterovirus A vaccine candidates for the prevention of hand, foot, and mouth disease.
Chih-Yeu Fang,Chia-Chyi Liu +1 more
TL;DR: A multivalent HFMD vaccine is required for broad protection against HFMD and variations of amino acid residues in these regions limit the induction of cross-neutralization antibodies, and therefore, an increase in the success in HFMD control is anticipated.
ComponentDOI
Atomic structures of enterovirus D68 in complex with two monoclonal antibodies define distinct mechanisms of viral neutralization
Qingbing Zheng,Rui Zhu,Longfa Xu,Maozhou He,X. Yan,X. Yan,Dongxiao Liu,Zhichao Yin,Y. Wu,Y. Li,L. Yang,W. Hou,Shaowei Li,Z. Li,Zhenqin Chen,Hai Yu,Y. Gu,Jun Zhang,Timothy S. Baker,Z.H. Zhou,Barney S. Graham,Tong Cheng,Ningshao Xia +22 more
TL;DR: The structures of three EV-D68 capsid states representing the virus at major phases are reported and two original monoclonal antibodies are described with distinct structurally defined mechanisms for virus neutralization.
ComponentDOI
Structures of Coxsackievirus A10 unveil the molecular mechanisms of receptor binding and viral uncoating
Ling Zhu,Yao Sun,Jinyan Fan,Bin Zhu,Lei Cao,Qiang Gao,Yanjun Zhang,Hongrong Liu,Zihe Rao,Zihe Rao,Xiangxi Wang +10 more
TL;DR: Structural comparisons coupled with previous results, reveal an ordered signal transmission process for enterovirus uncoating, converting exo-genetic receptor-attachment inputs into a generic RNA release mechanism.
Journal ArticleDOI
Clinical features and phylogenetic analysis of severe hand-foot-and-mouth disease caused by Coxsackievirus A6.
Xiaohan Yang,Yuanyuan Li,Changbin Zhang,Wenli Zhan,Jia Xie,Siqi Hu,Hui-Ying Chai,Pan Liu,Hongyu Zhao,Bin Tang,Keyi Chen,Jian Yu,Aihua Yin,Mingyong Luo +13 more
TL;DR: Genetic analyses showed all CA6 isolates belonged to lineage E2, and two amino acid changes of V174I and T283A in VP1 may be associated with the severity of HFMD.
References
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Phenix - a comprehensive python-based system for macromolecular structure solution
Paul D. Adams,Paul D. Adams,Pavel V. Afonine,Gábor Bunkóczi,Vincent B. Chen,Ian W. Davis,Nathaniel Echols,Jeffrey J. Headd,Li-Wei Hung,Gary J. Kapral,Ralf W. Grosse-Kunstleve,Airlie J. McCoy,Nigel W. Moriarty,Robert D. Oeffner,Randy J. Read,David S. Richardson,Jane S. Richardson,Thomas C. Terwilliger,Peter H. Zwart +18 more
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