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TitleNeutralizing antibodies can initiate genome release from human enterovirus 71.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 111, Issue 6, Page 2134-2139, Year 2014
Publish dateFeb 11, 2014
AuthorsPavel Plevka / Pei-Yin Lim / Rushika Perera / Jane Cardosa / Ampa Suksatu / Richard J Kuhn / Michael G Rossmann /
PubMed AbstractAntibodies were prepared by immunizing mice with empty, immature particles of human enterovirus 71 (EV71), a picornavirus that causes severe neurological disease in young children. The capsid ...Antibodies were prepared by immunizing mice with empty, immature particles of human enterovirus 71 (EV71), a picornavirus that causes severe neurological disease in young children. The capsid structure of these empty particles is different from that of the mature virus and is similar to "A" particles encountered when picornaviruses recognize a potential host cell before genome release. The monoclonal antibody E18, generated by this immunization, induced a conformational change when incubated at temperatures between 4 °C and 37 °C with mature virus, transforming infectious virions into A particles. The resultant loss of genome that was observed by cryo-EM and a fluorescent SYBR Green dye assay inactivated the virus, establishing the mechanism by which the virus is inactivated and demonstrating that the E18 antibody has potential as an anti-EV71 therapy. The antibody-mediated virus neutralization by the induction of genome release has not been previously demonstrated. Furthermore, the present results indicate that antibodies with genome-release activity could also be produced for other picornaviruses by immunization with immature particles.
External linksProc Natl Acad Sci U S A / PubMed:24469789 / PubMed Central
MethodsEM (single particle)
Resolution10.0 - 16.0 Å
Structure data

2397

4c0u

EMDB-2397, PDB-4c0u:
Cryo-EM reconstruction of enterovirus 71 in complex with a neutralizing antibody E18
Method: EM (single particle) / Resolution: 10.0 Å

2434

4c0y

EMDB-2434, PDB-4c0y:
Cryo-EM reconstruction of empty enterovirus 71 in complex with a neutralizing antibody E18
Method: EM (single particle) / Resolution: 16.0 Å

2436

4c10

EMDB-2436, PDB-4c10:
Cryo-EM reconstruction of empty enterovirus 71 in complex with a neutralizing antibody E19
Method: EM (single particle) / Resolution: 13.0 Å

Chemicals

ChemComp-SPH:
SPHINGOSINE / Sphingosine

ChemComp-NA:
Unknown entry

ChemComp-CL:
Unknown entry / Chloride

Source
  • mus musculus (house mouse)
  • human enterovirus 71
KeywordsVIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM COMPLEX / VIRUS / PATHOGEN / EV71 / ANTIBODY / E18 / NEUTRALIZING

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