Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28074040.
- Also identified by DOI 10.1073/pnas.1616502114 and PMC identifier 5278457.
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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.
Medical subject headings
- Antibodies, Neutralizing
- Hepatitis A virus