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Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site

DOI: 10.1073/pnas.1616502114 DOI Help

Authors: Xiangxi Wang (Institute of Biophysics, Chinese Academy of Science) , Ling Zhu (University of Oxford) , Minghao Dang (Institute of Biophysics, Chinese Academy of Sciences) , Zhongyu Hu (National Institutes for Food and Drug Control, Beijing) , Qiang Gao (Institute of Biophysics, Chinese Academy of Science) , Shuai Yuan (Institute of Biophysics, Chinese Academy of Science) , Yao Sun (Institute of Biophysics, Chinese Academy of Sciences) , Bo Zhang (Sinovac Biotech Co.) , Jingshan Ren (University of Oxford) , Abhay Kotecha (University of Oxford) , Thomas S. Walter (University of Oxford) , Junzhi Wang (National Institutes for Food and Drug Control, Beijing) , Elizabeth Fry (University of Oxford) , David I. Stuart (University of Oxford; Diamond Light Source) , Zihe Rao (Tsinghua University)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences

State: Published (Approved)
Published: January 2017

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 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.

Journal Keywords: picornavirus; entry; neutralizing mechanism; receptor recognition; uncoating

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography