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Published April 2013 | public
Journal Article

Intracellular Trafficking of an Antibody Bipolar Bridged Complex of HSV-1 gE-gI, IgG, and a Viral Antigen

Abstract

Herpes Simplex Virus 1 (HSV-1) glycoproteins, gE and gI, mimic a human Fcreceptor to hinder host immune responses. gE-gI binds the Fc region of human IgG (hIgG), which can be internalized and released into endocytic organelles. gE-gI also mediates antibody bipolar bridging (ABB), a process whereby IgG Fabs bind an antigen while its Fc region binds to gE-gI. The cellular fate of the ABB complex is unknown. Here, we engineered an in vitro system to determine whether ABB complexes are internalized and degraded in host cells. Human cell lines transiently expressing gE-gI and an HSV-1 antigen, gD, normally localized at the cell surface of HSV-1 virions and infected cells, were incubated with two forms of a monoclonal IgG anti-gD antibody: one with human Fc to allow ABB and one with mouse Fc, a control which binds gD but not gE-gI and cannot enable ABB. A hIgG against an irrelevant antigen was used as another non ABB control. 4D time-lapse confocal fluorescence data indicate that gD is internalized in an ABB specific fashion and internalization is dependent upon gE-gI. Internalized hIgGs bound to a surface viral antigen were targeted to lysosomes and biochemical analysis of enriched lysosomal compartments revealed degraded gD. These results suggest that gE-gI plays an active role in clearing the infected cell surface of both host IgG and viral antigens, providing HSV-1 with a mechanism to evade immune responses.

Additional Information

© 2013 FASEB.

Additional details

Created:
August 19, 2023
Modified:
October 24, 2023