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TitleStructural basis for neutralization of Japanese encephalitis virus by two potent therapeutic antibodies.
Journal, issue, pagesNat Microbiol, Vol. 3, Issue 3, Page 287-294, Year 2018
Publish dateJan 29, 2018
AuthorsXiaodi Qiu / Yingfeng Lei / Pan Yang / Qiang Gao / Nan Wang / Lei Cao / Shuai Yuan / Xiaofang Huang / Yongqiang Deng / Wenyu Ma / Tianbing Ding / Fanglin Zhang / Xingan Wu / Junjie Hu / Shan-Lu Liu / Chengfeng Qin / Xiangxi Wang / Zhikai Xu / Zihe Rao /
PubMed AbstractJapanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever and West Nile viruses, remains neglected and not well characterized . JEV is the leading causative agent of ...Japanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever and West Nile viruses, remains neglected and not well characterized . JEV is the leading causative agent of encephalitis, and is responsible for thousands of deaths each year in Asia. Humoral immunity is essential for protecting against flavivirus infections and passive immunization has been demonstrated to be effective in curing disease. Here, we demonstrate that JEV-specific monoclonal antibodies, 2F2 and 2H4, block attachment of the virus to its receptor and also prevent fusion of the virus. Neutralization of JEV by these antibodies is exceptionally potent and confers clear therapeutic benefit in mouse models. A single 20 μg dose of these antibodies resulted in 100% survival and complete clearance of JEV from the brains of mice. The 4.7 Å and 4.6 Å resolution cryo-electron microscopy structures of JEV-2F2-Fab and JEV-2H4-Fab complexes, together with the crystal structure of 2H4 Fab and our recent near-atomic structure of JEV , unveil the nature and location of epitopes targeted by the antibodies. Both 2F2 and 2H4 Fabs bind quaternary epitopes that span across three adjacent envelope proteins. Our results provide a structural and molecular basis for the application of 2F2 and 2H4 to treat JEV infection.
External linksNat Microbiol / PubMed:29379207
MethodsEM (single particle) / X-ray diffraction
Resolution2.206 - 4.7 Å
Structure data

6854

5ywo

EMDB-6854, PDB-5ywo:
Structure of JEV-2F2 Fab complex
Method: EM (single particle) / Resolution: 4.7 Å

6855

5ywp

EMDB-6855, PDB-5ywp:
JEV-2H4 Fab complex
Method: EM (single particle) / Resolution: 4.6 Å

PDB-5ywf:
Crystal structure of 2H4 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.206 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • japanese encephalitis virus
  • mus musculus (house mouse)
KeywordsIMMUNE SYSTEM / Flaviviruses / Viral encephalitis / neutralizing monoclonal antibodies / structural analysis / viral entry / VIRUS

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