Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein.
Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC) class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV) glycoprotein (GP) was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and β1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of β1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection.
Francica
Joseph R
JR
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
Varela-Rohena
Angel
A
Medvec
Andrew
A
Plesa
Gabriela
G
Riley
James L
JL
Bates
Paul
P
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019142:Hemorrhagic Fever, Ebola / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D019012:Integrin beta1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D019012:Integrin beta1; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus