Unknown

Dataset Information

0

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

altmetric image

Publications

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]

Similar Datasets

| S-EPMC5123051 | biostudies-literature
| S-EPMC4468474 | biostudies-literature
| S-EPMC6493668 | biostudies-literature
| S-EPMC4966830 | biostudies-literature
| S-EPMC4178804 | biostudies-literature
| S-EPMC7771633 | biostudies-literature
| S-EPMC6639266 | biostudies-literature
| S-EPMC3807900 | biostudies-literature
| S-EPMC6738269 | biostudies-literature
| S-EPMC5899191 | biostudies-literature