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rdf:type |
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lifeskim:mentions |
umls-concept:C0003320,
umls-concept:C0024518,
umls-concept:C0033684,
umls-concept:C0439662,
umls-concept:C0456387,
umls-concept:C0524637,
umls-concept:C0567416,
umls-concept:C0599894,
umls-concept:C0599896,
umls-concept:C1522240,
umls-concept:C1704259,
umls-concept:C1705987
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pubmed:issue |
4
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pubmed:dateCreated |
2011-1-21
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-10829079,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-10856251,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-10884920,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-11069884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-11905817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-12241714,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-12651740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-14532284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-14576817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-15044644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-15066634,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-15507720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-15596837,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-15596846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-15653685,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-15684323,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-15696119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-15795275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-17360652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-17378764,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-17620360,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-18094150,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-18204488,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-18977445,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-19119421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-19557156,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-19619657,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-19906905,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-20004735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-20543866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-2555554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-2981781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-3760563,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-667938,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-6975300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-7769726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-7799740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-8411362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-9310490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-9653172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21123379-9888696
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1098-5514
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
85
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1604-14
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pubmed:dateRevised |
2011-7-26
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pubmed:meshHeading |
pubmed-meshheading:21123379-Animals,
pubmed-meshheading:21123379-Antigen Presentation,
pubmed-meshheading:21123379-Cell Line,
pubmed-meshheading:21123379-Endocytosis,
pubmed-meshheading:21123379-Exocytosis,
pubmed-meshheading:21123379-Gene Expression Regulation,
pubmed-meshheading:21123379-HEK293 Cells,
pubmed-meshheading:21123379-Herpesvirus 4, Human,
pubmed-meshheading:21123379-Histocompatibility Antigens Class I,
pubmed-meshheading:21123379-Humans,
pubmed-meshheading:21123379-Mice,
pubmed-meshheading:21123379-Receptors, G-Protein-Coupled,
pubmed-meshheading:21123379-Signal Transduction,
pubmed-meshheading:21123379-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:21123379-Viral Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
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.
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pubmed:affiliation |
Cancer Research UK Birmingham Cancer Centre, University of Birmingham, Birmingham, United Kingdom.
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