51. Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.
- Author
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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, and Rao Z
- Subjects
- Animals, Antibodies, Monoclonal immunology, Binding Sites immunology, Capsid immunology, Capsid Proteins immunology, Female, Humans, Immunoglobulin Fab Fragments immunology, Mice, Mice, Inbred BALB C, Antibodies, Neutralizing immunology, Hepatitis A virus immunology
- 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., Competing Interests: The authors declare no conflict of interest.
- Published
- 2017
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