The Herpes Virus Fc Receptor gE-gI Mediates Antibody Bipolar Bridging to Clear Viral Antigens from the Cell Surface

PLoS Pathogens

Alexander H. Farley¹  Terri Lee¹  Pamela J. Bjorkman¹  Scott E. Fraser¹  Blaise Ndjamen¹ 

[1] Division of Biology and Biochemical Engineering, California Institute of Technology, Pasadena, California, United States of America

关键词: HeLa cells;    Lysosomes;    Antibodies;    Endosomes;    Endocytosis;    Cell binding;    Cell staining;    Genitourinary imaging;   

DOI  :  10.1371/journal.ppat.1003961

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY