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TitleSerotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 4419, Year 2020
Publish dateSep 4, 2020
AuthorsKang Wang / Binyang Zheng / Li Zhang / Lunbiao Cui / Xuan Su / Qian Zhang / Zhenxi Guo / Yu Guo / Wei Zhang / Ling Zhu / Fengcai Zhu / Zihe Rao / Xiangxi Wang /
PubMed AbstractEchovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and ...Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.
External linksNat Commun / PubMed:32887892 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.7 Å
Structure data

30303

7c80

EMDB-30303, PDB-7c80:
E30 F-particle in complex with 4B10
Method: EM (single particle) / Resolution: 3.7 Å

30304

7c81

EMDB-30304, PDB-7c81:
E30 F-particle in complex with 6C5
Method: EM (single particle) / Resolution: 3.1 Å

30408

7cmk

EMDB-30408, PDB-7cmk:
E30 E-particle in complex with 6C5
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-SPH:
SPHINGOSINE / Sphingosine

Source
  • mus musculus (house mouse)
  • echovirus e30
  • Mouse (mice)
KeywordsVIRUS/IMMUNE SYSTEM / MAb / 4B10 / E30 F-particle / VIRUS-IMMUNE SYSTEM complex / 6C5 / E30 / VIRUS / Echovirus B / mature / neutralizing MAb

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