The Herpes Virus Fc Receptor gE-gI Mediates Antibody Bipolar Bridging to Clear Viral Antigens from the Cell Surface: e1003961

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...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2014-03, Vol.10 (3)
Main Authors: Ndjamen, Blaise, Farley, Alexander H, Lee, Terri, Fraser, Scott E, Bjorkman, Pamela J
Format: Article
Language:English
Subjects:
Epidermal growth factor
Herpes simplex virus 1
Herpes viruses
Herpesvirus
Infections
Scholarships & fellowships
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1003961