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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Ndjamen B,Farley AH,Lee T,Fraser SE,Bjorkman PJ

doi

10.1371/journal.ppat.1003961

subject

Has Abstract

pub_date

2014-03-06 00:00:00

pages

e1003961

issue

3

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-13-02122

journal_volume

10

pub_type

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