Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16

He, Maozhou; Xu, Longfa; Zheng, Qingbing; Zhu, Rui; Yin, Zhichao; Zha, Zhenghui; Lin, Yulan; Yang, Lijie; Huang, Yang; Ye, X.; Li, S.; Hou, Wangheng; Wu, Yangtao; Han, Jian; Liu, Deyun; Li, Z.; Chen, Z.; Yu, Hai; Que, Yuqiong; Wang, Y.; Yan, Xiaodong; Zhang, Jun; Gu, Ying; Zhou, Z. Hong; Cheng, Tong; Xia, Ningshao

doi:10.1016/j.chom.2020.01.003

Cited by 26 publications

(63 citation statements)

References 65 publications

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“…As regards CV-A16, the mAb 18A7 bound to the BC, DE and HI loops of VP1 and partially overlapped with site 1; the mAb 14B10, binding to the threefold vertex between site 2 and site 3b, highly overlapped with site 3a (Fig. 3B,D) 36 . Specifically, it bound to the BC loop, EF loop of VP3 and some residues from neighboring VP2 BC, EF and HI loops.…”

Section: Resultsmentioning

confidence: 94%

“…3A,C). Gradually, three conformational epitopes of CV-A16 also have been unclosed, which were identified by mAbs 18A7, 14B10 and NA9D7, respectively 36 ( Fig. 3B,D).…”

Section: Resultsmentioning

confidence: 99%

“…receptors binding to virus; furthermore, they are the basis of viral antigenicity and used to distinguish the serotypes of enteroviruses 15,29 . Structural biology methods such as cryo-electron microscopy (Cryo-EM) and X-ray crystallography were used to determine the three-dimensional (3D) structure of the virus-Fab complexes and recognize the binding region (conformational epitope or called "footprint") of Fab with EV-A71 [30][31][32][33][34][35] or CV-A16 36 .…”

mentioning

confidence: 99%

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Bioinformatics-based prediction of conformational epitopes for Enterovirus A71 and Coxsackievirus A16

Wang

Zhu

Fang

et al. 2021

Sci Rep

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Enterovirus A71 (EV-A71), Coxsackievirus A16 (CV-A16) and CV-A10 are the major causative agents of hand, foot and mouth disease (HFMD). The conformational epitopes play a vital role in monitoring the antigenic evolution, predicting dominant strains and preparing vaccines. In this study, we employed a Bioinformatics-based algorithm to predict the conformational epitopes of EV-A71 and CV-A16 and compared with that of CV-A10. Prediction results revealed that the distribution patterns of conformational epitopes of EV-A71 and CV-A16 were similar to that of CV-A10 and their epitopes likewise consisted of three sites: site 1 (on the “north rim” of the canyon around the fivefold vertex), site 2 (on the “puff”) and site 3 (one part was in the “knob” and the other was near the threefold vertex). The reported epitopes highly overlapped with our predicted epitopes indicating the predicted results were reliable. These data suggested that three-site distribution pattern may be the basic distribution role of epitopes on the enteroviruses capsids. Our prediction results of EV-A71 and CV-A16 can provide essential information for monitoring the antigenic evolution of enterovirus.

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Section: Resultsmentioning

confidence: 94%

“…3A,C). Gradually, three conformational epitopes of CV-A16 also have been unclosed, which were identified by mAbs 18A7, 14B10 and NA9D7, respectively 36 ( Fig. 3B,D).…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Bioinformatics-based prediction of conformational epitopes for Enterovirus A71 and Coxsackievirus A16

Wang

Zhu

Fang

et al. 2021

Sci Rep

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“…Sub-particle refinement approaches have made possible higher resolution maps of large, flexible virus capsids (Bhella, 2019;Chen et al, 2018;Zhu et al, 2018). Atomic resolution structures of virus-Fab complexes can elucidate mechanisms of neutralization and define conformational epitopes on the capsid, including key residues involved in recognition by the antibody (Dong et al, 2017;He et al, 2020;Zhu et al, 2018). Virus-Fab complex structures may predict viable escape mutations that naturally emerge under selective pressure from nAbs.…”

Section: Introductionmentioning

confidence: 99%

Antibody escape by polyomavirus capsid mutation facilitates neurovirulence

Lauver

Goetschius

Netherby

et al. 2020

eLife

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JCPyV polyomavirus, a member of the human virome, causes Progressive Multifocal Leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo EM and a custom sub-particle refinement approach, we resolved an MuPyV:Fab complex map to 3.2 Å resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation.

show abstract

“…Subparticle refinement approaches have made possible higher resolution maps of large, flexible virus capsids (Bhella, 2019;Chen et al, 2018;Zhu et al, 2018). Atomic resolution structures of virus-Fab complexes can elucidate mechanisms of neutralization and define conformational epitopes on the capsid, including key residues involved in recognition by the antibody (Dong et al, 2017;He et al, 2020;Zhu et al, 2018). Virus-Fab complex structures may predict viable escape mutations that naturally emerge under selective pressure from nAbs.…”

Section: Introductionmentioning

confidence: 99%

Antibody Escape by Polyomavirus Capsid Mutation Facilitates Neurovirulence

Lauver

Goetschius

Netherby

et al. 2020

Preprint

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JCPyV polyomavirus, a member of the human virome, causes Progressive Multifocal Leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo EM and a custom subvolume refinement approach, we resolved an MuPyV:Fab complex map to 3.1 Angstrom resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation.

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Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16

Cited by 26 publications

References 65 publications

Bioinformatics-based prediction of conformational epitopes for Enterovirus A71 and Coxsackievirus A16

Bioinformatics-based prediction of conformational epitopes for Enterovirus A71 and Coxsackievirus A16

Antibody escape by polyomavirus capsid mutation facilitates neurovirulence

Antibody Escape by Polyomavirus Capsid Mutation Facilitates Neurovirulence

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