The Epstein-Barr virus-encoded BILF1 protein modulates immune recognition of endogenously processed antigen by targeting major histocompatibility complex class I molecules trafficking on both the exocytic and endocytic pathways
Despite triggering strong immune responses, Epstein-Barr virus (EBV) has colonized more than 90% of the adult human population. Successful persistence of EBV depends on the establishment of a balance between host immune responses and viral immune evasion. Here we have extended our studies on the EBV-encoded BILF1 protein, which was recently identified as an immunoevasin that functions by enhancing degradation of major histocompatibility complex class I (MHC-I) antigens via lysosomes. We now demonstrate that disruption of the EKT signaling motif of BILF1 by a K122A mutation impairs the ability of BILF1 to enhance endocytosis of surface MHC-I molecules, while subsequent lysosomal degradation was impaired by deletion of the 21-residue C-terminal tail of BILF1. Furthermore, we identified another mechanism of BILF1 immunomodulation: it targets newly synthesized MHC-I/peptide complexes en route to the cell surface. Importantly, although the diversion of MHC-I on the exocytic pathway caused a relatively modest reduction in cell surface MHC-I, presentation of endogenously processed target peptides to immune CD8(+) effector T cells was reduced by around 65%. The immune-modulating functions of BILF1 in the context of the whole virus were confirmed in cells lytically infected with a recombinant EBV in which BILF1 was deleted. This study therefore extends our initial observations on BILF1 to show that this immunoevasin can target MHC-I antigen presentation via both the exocytic and endocytic trafficking pathways. The results also emphasize the merits of including functional T cell recognition assays to gain a more complete picture of immunoevasin effects on the antigen presentation pathway.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2011 |
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Erschienen: |
2011 |
Enthalten in: |
Zur Gesamtaufnahme - volume:85 |
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Enthalten in: |
Journal of virology - 85(2011), 4 vom: 01. Feb., Seite 1604-14 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zuo, Jianmin [VerfasserIn] |
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Links: |
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Themen: |
BILF1 protein, Epstein-Barr virus |
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Anmerkungen: |
Date Completed 07.03.2011 Date Revised 27.05.2023 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1128/JVI.01608-10 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM204030501 |
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520 | |a Despite triggering strong immune responses, Epstein-Barr virus (EBV) has colonized more than 90% of the adult human population. Successful persistence of EBV depends on the establishment of a balance between host immune responses and viral immune evasion. Here we have extended our studies on the EBV-encoded BILF1 protein, which was recently identified as an immunoevasin that functions by enhancing degradation of major histocompatibility complex class I (MHC-I) antigens via lysosomes. We now demonstrate that disruption of the EKT signaling motif of BILF1 by a K122A mutation impairs the ability of BILF1 to enhance endocytosis of surface MHC-I molecules, while subsequent lysosomal degradation was impaired by deletion of the 21-residue C-terminal tail of BILF1. Furthermore, we identified another mechanism of BILF1 immunomodulation: it targets newly synthesized MHC-I/peptide complexes en route to the cell surface. Importantly, although the diversion of MHC-I on the exocytic pathway caused a relatively modest reduction in cell surface MHC-I, presentation of endogenously processed target peptides to immune CD8(+) effector T cells was reduced by around 65%. The immune-modulating functions of BILF1 in the context of the whole virus were confirmed in cells lytically infected with a recombinant EBV in which BILF1 was deleted. This study therefore extends our initial observations on BILF1 to show that this immunoevasin can target MHC-I antigen presentation via both the exocytic and endocytic trafficking pathways. The results also emphasize the merits of including functional T cell recognition assays to gain a more complete picture of immunoevasin effects on the antigen presentation pathway | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a BILF1 protein, Epstein-Barr virus |2 NLM | |
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650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
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700 | 1 | |a Quinn, Laura L |e verfasserin |4 aut | |
700 | 1 | |a Tamblyn, Jennifer |e verfasserin |4 aut | |
700 | 1 | |a Thomas, Wendy A |e verfasserin |4 aut | |
700 | 1 | |a Feederle, Regina |e verfasserin |4 aut | |
700 | 1 | |a Delecluse, Henri-Jacques |e verfasserin |4 aut | |
700 | 1 | |a Hislop, Andrew D |e verfasserin |4 aut | |
700 | 1 | |a Rowe, Martin |e verfasserin |4 aut | |
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