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TitlePotent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 114, Issue 4, Page 770-775, Year 2017
Publish dateJan 24, 2017
AuthorsXiangxi 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 AbstractHepatitis 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 linksProc Natl Acad Sci U S A / PubMed:28074040 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.907 - 4.2 Å
Structure data

6686

5wte

EMDB-6686, PDB-5wte:
Cryo-EM structure for Hepatitis A virus full particle
Method: EM (single particle) / Resolution: 3.4 Å

6687

5wtf

EMDB-6687, PDB-5wtf:
Cryo-EM structure for Hepatitis A virus empty particle
Method: EM (single particle) / Resolution: 3.9 Å

6688

5wth

EMDB-6688, PDB-5wth:
Cryo-EM structure for Hepatitis A virus complexed with FAB
Method: EM (single particle) / Resolution: 4.2 Å

PDB-5wtg:
Crystal structure of the Fab fragment of anti-HAV antibody R10
Method: X-RAY DIFFRACTION / Resolution: 2.907 Å

Source
  • hepatovirus a
  • hepatitis a virus
  • mus musculus (house mouse)
KeywordsVIRUS / HAV / Neutralizing mechanism / Receptor recognition / Viral entry / IMMUNE SYSTEM

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