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TitleAtomic structures of enterovirus D68 in complex with two monoclonal antibodies define distinct mechanisms of viral neutralization.
Journal, issue, pagesNat Microbiol, Vol. 4, Issue 1, Page 124-133, Year 2019
Publish dateNov 5, 2018
AuthorsQingbing Zheng / Rui Zhu / Longfa Xu / Maozhou He / Xiaodong Yan / Dongxiao Liu / Zhichao Yin / Yangtao Wu / Yongchao Li / Lisheng Yang / Wangheng Hou / Shuxuan Li / Zizhen Li / Zhenqin Chen / Zhihai Li / Hai Yu / Ying Gu / Jun Zhang / Timothy S Baker / Z Hong Zhou / Barney S Graham / Tong Cheng / Shaowei Li / Ningshao Xia /
PubMed AbstractEnterovirus D68 (EV-D68) undergoes structural transformation between mature, cell-entry intermediate (A-particle) and empty forms throughout its life cycle. Structural information for the various ...Enterovirus D68 (EV-D68) undergoes structural transformation between mature, cell-entry intermediate (A-particle) and empty forms throughout its life cycle. Structural information for the various forms and antibody-bound capsids will facilitate the development of effective vaccines and therapeutics against EV-D68 infection, which causes childhood respiratory and paralytic diseases worldwide. Here, we report the structures of three EV-D68 capsid states representing the virus at major phases. We further describe two original monoclonal antibodies (15C5 and 11G1) with distinct structurally defined mechanisms for virus neutralization. 15C5 and 11G1 engage the capsid loci at icosahedral three-fold and five-fold axes, respectively. To block viral attachment, 15C5 binds three forms of capsids, and triggers mature virions to transform into A-particles, mimicking engagement by the functional receptor ICAM-5, whereas 11G1 exclusively recognizes the A-particle. Our data provide a structural and molecular explanation for the transition of picornavirus capsid conformations and demonstrate distinct mechanisms for antibody-mediated neutralization.
External linksNat Microbiol / PubMed:30397341 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 7.2 Å
Structure data

EMDB-9629, PDB-6aj0:
The structure of Enterovirus D68 mature virion
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-9631, PDB-6aj2:
The structure of ICAM-5 triggered Enterovirus D68 virus A-particle
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-9632, PDB-6aj3:
The structure of Enterovirus D68 procapsid
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-9633, PDB-6aj7:
The structure of Enterovirus D68 mature virion in complex with Fab 15C5
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-9634, PDB-6aj9:
The structure of Enterovirus D68 mature virion in complex with Fab 15C5 and 11G1
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-9635:
The structure of Enterovirus D68 A-particle triggered by an unknown stimulus
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-9636:
The structure of Enterovirus D68 A-particle in complex with Fab 11G1
Method: EM (single particle) / Resolution: 7.2 Å

Source
  • enterovirus d68
  • mus musculus (house mouse)
KeywordsVIRUS / Enterovirus D68 / mature virion / ICAM-5 / A-paticle / procapsid / neutralizing antibody / Immune-complex

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