CaltechAUTHORS
  A Caltech Library Service

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

Ndjamen, Blaise and Farley, Alexander H. and Lee, Terri and Fraser, Scott E. and Bjorkman, Pamela J. (2014) The Herpes Virus Fc Receptor gE-gI Mediates Antibody Bipolar Bridging to Clear Viral Antigens from the Cell Surface. PLoS Pathogens, 10 (3). Art. No. e1003961. ISSN 1553-7366. PMCID PMC3946383. https://resolver.caltech.edu/CaltechAUTHORS:20140718-092549260

[img]
Preview
PDF - Published Version
Creative Commons Attribution.

2407Kb
[img]
Preview
Image (TIFF) (Figure S1) - Supplemental Material
Creative Commons Attribution.

13Mb
[img]
Preview
Image (TIFF) (Figure S2) - Supplemental Material
Creative Commons Attribution.

9Mb
[img]
Preview
Image (TIFF) (Figure S3) - Supplemental Material
Creative Commons Attribution.

9Mb
[img]
Preview
Image (TIFF) (Figure S4) - Supplemental Material
Creative Commons Attribution.

1359Kb
[img] Video (AVI) (Movie S1) - Supplemental Material
Creative Commons Attribution.

21Mb
[img] Video (AVI) (Movie S2) - Supplemental Material
Creative Commons Attribution.

6Mb
[img] Video (AVI) (Movie S3) - Supplemental Material
Creative Commons Attribution.

14Mb
[img] Video (AVI) (Movie S4) - Supplemental Material
Creative Commons Attribution.

17Mb
[img] Video (AVI) (Movie S5) - Supplemental Material
Creative Commons Attribution.

14Mb
[img] Video (AVI) (Movie S6) - Supplemental Material
Creative Commons Attribution.

15Mb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20140718-092549260

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.ppat.1003961DOIArticle
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003961PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946383/PubMed CentralArticle
ORCID:
AuthorORCID
Fraser, Scott E.0000-0002-5377-0223
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2014 Ndjamen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received August 14, 2013; Accepted January 16, 2014; Published March 6, 2014. Editor: Roger D. Everett, University of Glasgow, United Kingdom. This work was supported by the National Institutes of Health (5 R37 AI041239-15 to PJB, http://www.nih.gov/) and the Irvington Institute Fellowship Program of the Cancer Research Institute (postdoctoral fellowship to BN, http://www.cancerresearch.org/grants-programs/grants-fellowships). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. We thank Homayon Ghiasi for gE, gI, and gD genes, Stephen Mayfield for HSV8 anti-gD antibody genes, Sean Megason for the Cerulean gene, Malini Raghavan for the 2E9 anti-gI antibody, the Caltech Protein Expression Center for expression of antibodies used for internalization, Yunji Wu for purified 2G12 IgG, Kathryn E. Huey-Tubman for assistance obtaining reagents, Marta Murphy for help making figures, and members of the Bjorkman lab for critical reading of the manuscript. Author Contributions: Conceived and designed the experiments: BN AHF PJB. Performed the experiments: BN AHF TL. Analyzed the data: BN TL SEF PJB. Contributed reagents/materials/analysis tools: BN AHF TL SEF PJB. Wrote the paper: BN AHF PJB. Constructed the antibody bipolar bridging system components: BN AHF. Performed confocal fluorescence imaging and live cell microscopy: BN. Conducted subcellular fractionation and western blot analyses: BN TL. Analyzed results: BN AHF SEF PJB.
Funders:
Funding AgencyGrant Number
NIH5 R37 AI041239-15
Cancer Research InstituteUNSPECIFIED
Issue or Number:3
PubMed Central ID:PMC3946383
Record Number:CaltechAUTHORS:20140718-092549260
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20140718-092549260
Official Citation:Ndjamen B, Farley AH, Lee T, Fraser SE, Bjorkman PJ (2014) The Herpes Virus Fc Receptor gE-gI Mediates Antibody Bipolar Bridging to Clear Viral Antigens from the Cell Surface. PLoS Pathog 10(3): e1003961. doi:10.1371/journal.ppat.1003961
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:47320
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:18 Jul 2014 17:00
Last Modified:03 Oct 2019 06:52

Repository Staff Only: item control page