title: The herpes virus Fc receptor gE-gI mediates antibody bipolar bridging to clear viral antigens from the cell surface.
abstract: The Herpes Simplex Virus 1 (HSV-1) glycoprotein gE-gI is a transmembrane Fc receptor found on the surface of infected cells and virions that binds human immunoglobulin G (hIgG). gE-gI can also participate in antibody bipolar bridging (ABB), a process by which the antigen-binding fragments (Fabs) of the IgG bind a viral antigen while the Fc binds to gE-gI. IgG Fc binds gE-gI at basic, but not acidic, pH, suggesting that IgG bound at extracellular pH by cell surface gE-gI would dissociate and be degraded in acidic endosomes/lysosomes if endocytosed. The fate of viral antigens associated with gE-gI-bound IgG had been unknown: they could remain at the cell surface or be endocytosed with IgG. Here, we developed an in vitro model system for ABB and investigated the trafficking of ABB complexes using 4-D confocal fluorescence imaging of ABB complexes with transferrin or epidermal growth factor, well-characterized intracellular trafficking markers. Our data showed that cells expressing gE-gI and the viral antigen HSV-1 gD endocytosed anti-gD IgG and gD in a gE-gI-dependent process, resulting in lysosomal localization. These results suggest that gE-gI can mediate clearance of infected cell surfaces of anti-viral host IgG and viral antigens to evade IgG-mediated responses, representing a general mechanism for viral Fc receptors in immune evasion and viral pathogenesis.
authors.affiliation: Division of Biology and Biochemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Blaise
authors.initials: B
authors.lastname: Ndjamen
authors.affiliation: Division of Biology and Biochemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Farley
authors.affiliation: Division of Biology and Biochemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Terri
authors.initials: T
authors.lastname: Lee
authors.affiliation: Division of Biology and Biochemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Fraser
authors.affiliation: Division of Biology and Biochemical Engineering, California Institute of Technology, Pasadena, California, United States of America; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D018613:Microscopy, Confocal; D011961:Receptors, Fc / Q000276:immunology*; D014162:Transfection; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D011961:Receptors, Fc; D014764:Viral Proteins