title: Antibody recognition of cell surface-associated NS1 triggers Fc-gamma receptor-mediated phagocytosis and clearance of West Nile Virus-infected cells.
abstract: 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.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Chung
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Thompson
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology*; D011485:Protein Binding; D017452:Receptors, IgG / Q000276:immunology*; D016019:Survival Analysis; D017361:Viral Nonstructural Proteins / Q000276:immunology* / Q000378:metabolism; D014901:West Nile Fever / Q000276:immunology; D014902:West Nile virus / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C100315:NS1 protein, Flavivirus; D017452:Receptors, IgG; D017361:Viral Nonstructural Proteins