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-Structure paper
Title | Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site. |
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Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 114, Issue 4, Page 770-775, Year 2017 |
Publish date | Jan 24, 2017 |
Authors | Xiangxi Wang / Ling Zhu / Minghao Dang / Zhongyu Hu / Qiang Gao / Shuai Yuan / Yao Sun / Bo Zhang / Jingshan Ren / Abhay Kotecha / Thomas S Walter / Junzhi Wang / Elizabeth E Fry / David I Stuart / Zihe Rao / |
PubMed Abstract | Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and ...Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention. |
External links | Proc Natl Acad Sci U S A / PubMed:28074040 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.907 - 4.2 Å |
Structure data | EMDB-6686, PDB-5wte: EMDB-6687, PDB-5wtf: EMDB-6688, PDB-5wth: PDB-5wtg: |
Source |
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Keywords | VIRUS / HAV / Neutralizing mechanism / Receptor recognition / Viral entry / IMMUNE SYSTEM |