The molecular basis of antibody-mediated neutralization of West Nile virus

Abstract

The study of the interaction between the West Nile virus envelope protein and monoclonal antibodies has provided insight into the molecular mechanisms of neutralization. Structural studies have identified an epitope on the lateral ridge of domain III of the West Nile virus E protein that is recognized by antibodies with the strongest neutralizing activity in vitro and in vivo. Antibodies that bind to this epitope are particularly inhibitory because they block infection at a post-attachment step and at concentrations that result in a low occupancy of the available sites on the virion.

Keywords::

• affinity
• antibody
• antibody-dependent enhancement
• epitope
• neutralization
• West Nile virus

Acknowledgments

The authors would like to thank K Austin and G Nybakken for help with figure preparation and D Fremont and T Pierson for helpful discussions. Work in our laboratory is supported by the Pediatric Dengue Vaccine Initiative and the NIH (grants AI061373 and U54 AI057160).