Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site
Wang X., Zhu L., Dang M., Hu Z., Gao Q., Yuan S., Sun Y., Zhang B., Ren J., Kotecha A., Walter TS., Wang J., Fry EE., Stuart DI., Rao Z.
Significance Hepatitis A virus (HAV) remains enigmatic, being unusually stable physically. Where the receptor binds and how the virion can be destabilized to release the genome are unknown. We report a potent HAV-specific neutralizing monoclonal antibody, R10, that blocks receptor attachment and interferes with viral uncoating. We have determined high-resolution cryo-EM structures of HAV full particles, empty particles, and full particles complexed with R10 Fab, revealing that R10 binds to the viral surface along the edges of the pentameric building block of the virus, and these interactions are critical for receptor binding and viral uncoating. Our results point to the use of a receptor mimic mechanism to neutralize virus infection, highlighting new opportunities for therapeutic intervention.