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

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.

SUBMITTER: Wang X

PROVIDER: S-EPMC5278457 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Wang Xiangxi X Zhu Ling L Dang Minghao M Hu Zhongyu Z Gao Qiang Q Yuan Shuai S Sun Yao Y Zhang Bo B Ren Jingshan J Kotecha Abhay A Walter Thomas S TS Wang Junzhi J Fry Elizabeth E EE Stuart David I DI Rao Zihe Z

Proceedings of the National Academy of Sciences of the United States of America 20170110 4

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 ...[more]

PMID: 28074040

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

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

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