Author:
Wang Xiangxi,Zhu Ling,Dang Minghao,Hu Zhongyu,Gao Qiang,Yuan Shuai,Sun Yao,Zhang Bo,Ren Jingshan,Kotecha Abhay,Walter Thomas S.,Wang Junzhi,Fry Elizabeth E.,Stuart David I.,Rao Zihe
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.
Funder
National Science Foundation
Publisher
Proceedings of the National Academy of Sciences
Cited by
41 articles.
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