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The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells

Cell-mediated immunity plays a key role in host control of viral infection. This is exemplified by life-threatening reactivations of e.g. herpesviruses in individuals with impaired T-cell and/or iNKT cell responses. To allow lifelong persistence and virus production in the face of primed immunity, h...

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Autores principales: Gram, Anna M., Oosenbrug, Timo, Lindenbergh, Marthe F. S., Büll, Christian, Comvalius, Anouskha, Dickson, Kathryn J. I., Wiegant, Joop, Vrolijk, Hans, Lebbink, Robert Jan, Wolterbeek, Ron, Adema, Gosse J., Griffioen, Marieke, Heemskerk, Mirjam H. M., Tscharke, David C., Hutt-Fletcher, Lindsey M., Wiertz, Emmanuel J. H. J., Hoeben, Rob C., Ressing, Maaike E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831753/
https://www.ncbi.nlm.nih.gov/pubmed/27077376
http://dx.doi.org/10.1371/journal.ppat.1005550
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author Gram, Anna M.
Oosenbrug, Timo
Lindenbergh, Marthe F. S.
Büll, Christian
Comvalius, Anouskha
Dickson, Kathryn J. I.
Wiegant, Joop
Vrolijk, Hans
Lebbink, Robert Jan
Wolterbeek, Ron
Adema, Gosse J.
Griffioen, Marieke
Heemskerk, Mirjam H. M.
Tscharke, David C.
Hutt-Fletcher, Lindsey M.
Wiertz, Emmanuel J. H. J.
Hoeben, Rob C.
Ressing, Maaike E.
author_facet Gram, Anna M.
Oosenbrug, Timo
Lindenbergh, Marthe F. S.
Büll, Christian
Comvalius, Anouskha
Dickson, Kathryn J. I.
Wiegant, Joop
Vrolijk, Hans
Lebbink, Robert Jan
Wolterbeek, Ron
Adema, Gosse J.
Griffioen, Marieke
Heemskerk, Mirjam H. M.
Tscharke, David C.
Hutt-Fletcher, Lindsey M.
Wiertz, Emmanuel J. H. J.
Hoeben, Rob C.
Ressing, Maaike E.
author_sort Gram, Anna M.
collection PubMed
description Cell-mediated immunity plays a key role in host control of viral infection. This is exemplified by life-threatening reactivations of e.g. herpesviruses in individuals with impaired T-cell and/or iNKT cell responses. To allow lifelong persistence and virus production in the face of primed immunity, herpesviruses exploit immune evasion strategies. These include a reduction in viral antigen expression during latency and a number of escape mechanisms that target antigen presentation pathways. Given the plethora of foreign antigens expressed in virus-producing cells, herpesviruses are conceivably most vulnerable to elimination by cell-mediated immunity during the replicative phase of infection. Here, we show that a prototypic herpesvirus, Epstein-Barr virus (EBV), encodes a novel, broadly acting immunoevasin, gp150, that is expressed during the late phase of viral replication. In particular, EBV gp150 inhibits antigen presentation by HLA class I, HLA class II, and the non-classical, lipid-presenting CD1d molecules. The mechanism of gp150-mediated T-cell escape does not depend on degradation of the antigen-presenting molecules nor does it require gp150’s cytoplasmic tail. Through its abundant glycosylation, gp150 creates a shield that impedes surface presentation of antigen. This is an unprecedented immune evasion mechanism for herpesviruses. In view of its likely broader target range, gp150 could additionally have an impact beyond escape of T cell activation. Importantly, B cells infected with a gp150-null mutant EBV displayed rescued levels of surface antigen presentation by HLA class I, HLA class II, and CD1d, supporting an important role for iNKT cells next to classical T cells in fighting EBV infection. At the same time, our results indicate that EBV gp150 prolongs the timespan for producing viral offspring at the most vulnerable stage of the viral life cycle.
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spelling pubmed-48317532016-04-22 The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells Gram, Anna M. Oosenbrug, Timo Lindenbergh, Marthe F. S. Büll, Christian Comvalius, Anouskha Dickson, Kathryn J. I. Wiegant, Joop Vrolijk, Hans Lebbink, Robert Jan Wolterbeek, Ron Adema, Gosse J. Griffioen, Marieke Heemskerk, Mirjam H. M. Tscharke, David C. Hutt-Fletcher, Lindsey M. Wiertz, Emmanuel J. H. J. Hoeben, Rob C. Ressing, Maaike E. PLoS Pathog Research Article Cell-mediated immunity plays a key role in host control of viral infection. This is exemplified by life-threatening reactivations of e.g. herpesviruses in individuals with impaired T-cell and/or iNKT cell responses. To allow lifelong persistence and virus production in the face of primed immunity, herpesviruses exploit immune evasion strategies. These include a reduction in viral antigen expression during latency and a number of escape mechanisms that target antigen presentation pathways. Given the plethora of foreign antigens expressed in virus-producing cells, herpesviruses are conceivably most vulnerable to elimination by cell-mediated immunity during the replicative phase of infection. Here, we show that a prototypic herpesvirus, Epstein-Barr virus (EBV), encodes a novel, broadly acting immunoevasin, gp150, that is expressed during the late phase of viral replication. In particular, EBV gp150 inhibits antigen presentation by HLA class I, HLA class II, and the non-classical, lipid-presenting CD1d molecules. The mechanism of gp150-mediated T-cell escape does not depend on degradation of the antigen-presenting molecules nor does it require gp150’s cytoplasmic tail. Through its abundant glycosylation, gp150 creates a shield that impedes surface presentation of antigen. This is an unprecedented immune evasion mechanism for herpesviruses. In view of its likely broader target range, gp150 could additionally have an impact beyond escape of T cell activation. Importantly, B cells infected with a gp150-null mutant EBV displayed rescued levels of surface antigen presentation by HLA class I, HLA class II, and CD1d, supporting an important role for iNKT cells next to classical T cells in fighting EBV infection. At the same time, our results indicate that EBV gp150 prolongs the timespan for producing viral offspring at the most vulnerable stage of the viral life cycle. Public Library of Science 2016-04-14 /pmc/articles/PMC4831753/ /pubmed/27077376 http://dx.doi.org/10.1371/journal.ppat.1005550 Text en © 2016 Gram et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Gram, Anna M.
Oosenbrug, Timo
Lindenbergh, Marthe F. S.
Büll, Christian
Comvalius, Anouskha
Dickson, Kathryn J. I.
Wiegant, Joop
Vrolijk, Hans
Lebbink, Robert Jan
Wolterbeek, Ron
Adema, Gosse J.
Griffioen, Marieke
Heemskerk, Mirjam H. M.
Tscharke, David C.
Hutt-Fletcher, Lindsey M.
Wiertz, Emmanuel J. H. J.
Hoeben, Rob C.
Ressing, Maaike E.
The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells
title The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells
title_full The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells
title_fullStr The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells
title_full_unstemmed The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells
title_short The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells
title_sort epstein-barr virus glycoprotein gp150 forms an immune-evasive glycan shield at the surface of infected cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831753/
https://www.ncbi.nlm.nih.gov/pubmed/27077376
http://dx.doi.org/10.1371/journal.ppat.1005550
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