Antibody Recognition of Cell Surface-Associated NS1 Triggers Fc-γ Receptor-Mediated Phagocytosis and Clearance of West Nile Virus-Infected Cells

Previous studies have suggested that monoclonal antibodies (MAbs) to flavivirus nonstructural protein-1 (NS-1) protect against infection in mice through an Fc-gamma receptor-dependent pathway. To identify a specific mechanism, we evaluated the protective activity of anti-NS1 MAbs to WNV using mice and cells with deficiencies of specific Fc-gamma receptors. Our results suggest that only MAbs that recognize cell surface-associated NS1 trigger Fc-gamma receptor I- and/or IV-mediated phagocytosis and clearance of WNV-infected cells. These findings may be relevant for generating novel therapeutic MAbs or vaccines against flaviviruses that target the NS1 protein.