Antibody recognition of cell surface-associated NS1 triggers Fc-gamma 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.
Chung
Kyung Min
KM
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Thompson
Bruce S
BS
Fremont
Daved H
DH
Diamond
Michael S
MS
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*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C100315:NS1 protein, Flavivirus; D017452:Receptors, IgG; D017361:Viral Nonstructural Proteins