The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.

Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of seconda...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ildar Gabaev, Lars Steinbrück, Claudia Pokoyski, Andreas Pich, Richard J Stanton, Reinhard Schwinzer, Thomas F Schulz, Roland Jacobs, Martin Messerle, Penelope C Kay-Fedorov
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0cb876d627b3413fb328cb0e678021eb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0cb876d627b3413fb328cb0e678021eb
record_format	dspace
spelling	oai:doaj.org-article:0cb876d627b3413fb328cb0e678021eb2021-11-18T06:04:59ZThe human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.1553-73661553-737410.1371/journal.ppat.1002432https://doaj.org/article/0cb876d627b3413fb328cb0e678021eb2011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174689/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of secondary infections in patients with weakened or immature immune systems. In a search for new immunomodulatory proteins, we investigated the UL11 protein, a member of the CMV RL11 family. This protein family is defined by the RL11 domain, which has homology to immunoglobulin domains and adenoviral immunomodulatory proteins. We show that pUL11 is expressed on the cell surface and induces intercellular interactions with leukocytes. This was demonstrated to be due to the interaction of pUL11 with the receptor tyrosine phosphatase CD45, identified by mass spectrometry analysis of pUL11-associated proteins. CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. CD45 has a pivotal function regulating T cell signaling thresholds; in its absence, the Src family kinase Lck is inactive and signaling through the T cell receptor (TCR) is therefore shut off. In the presence of pUL11, several CD45-mediated functions were inhibited. The induction of tyrosine phosphorylation of multiple signaling proteins upon TCR stimulation was reduced and T cell proliferation was impaired. We therefore conclude that pUL11 has immunosuppressive properties, and that disruption of T cell function via inhibition of CD45 is a previously unknown immunomodulatory strategy of CMV.Ildar GabaevLars SteinbrückClaudia PokoyskiAndreas PichRichard J StantonReinhard SchwinzerThomas F SchulzRoland JacobsMartin MesserlePenelope C Kay-FedorovPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 12, p e1002432 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ildar Gabaev Lars Steinbrück Claudia Pokoyski Andreas Pich Richard J Stanton Reinhard Schwinzer Thomas F Schulz Roland Jacobs Martin Messerle Penelope C Kay-Fedorov The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.
description	Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of secondary infections in patients with weakened or immature immune systems. In a search for new immunomodulatory proteins, we investigated the UL11 protein, a member of the CMV RL11 family. This protein family is defined by the RL11 domain, which has homology to immunoglobulin domains and adenoviral immunomodulatory proteins. We show that pUL11 is expressed on the cell surface and induces intercellular interactions with leukocytes. This was demonstrated to be due to the interaction of pUL11 with the receptor tyrosine phosphatase CD45, identified by mass spectrometry analysis of pUL11-associated proteins. CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. CD45 has a pivotal function regulating T cell signaling thresholds; in its absence, the Src family kinase Lck is inactive and signaling through the T cell receptor (TCR) is therefore shut off. In the presence of pUL11, several CD45-mediated functions were inhibited. The induction of tyrosine phosphorylation of multiple signaling proteins upon TCR stimulation was reduced and T cell proliferation was impaired. We therefore conclude that pUL11 has immunosuppressive properties, and that disruption of T cell function via inhibition of CD45 is a previously unknown immunomodulatory strategy of CMV.
format	article
author	Ildar Gabaev Lars Steinbrück Claudia Pokoyski Andreas Pich Richard J Stanton Reinhard Schwinzer Thomas F Schulz Roland Jacobs Martin Messerle Penelope C Kay-Fedorov
author_facet	Ildar Gabaev Lars Steinbrück Claudia Pokoyski Andreas Pich Richard J Stanton Reinhard Schwinzer Thomas F Schulz Roland Jacobs Martin Messerle Penelope C Kay-Fedorov
author_sort	Ildar Gabaev
title	The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.
title_short	The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.
title_full	The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.
title_fullStr	The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.
title_full_unstemmed	The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.
title_sort	human cytomegalovirus ul11 protein interacts with the receptor tyrosine phosphatase cd45, resulting in functional paralysis of t cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/0cb876d627b3413fb328cb0e678021eb
work_keys_str_mv	AT ildargabaev thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT larssteinbruck thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT claudiapokoyski thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT andreaspich thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT richardjstanton thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT reinhardschwinzer thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT thomasfschulz thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT rolandjacobs thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT martinmesserle thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT penelopeckayfedorov thehumancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT ildargabaev humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT larssteinbruck humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT claudiapokoyski humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT andreaspich humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT richardjstanton humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT reinhardschwinzer humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT thomasfschulz humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT rolandjacobs humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT martinmesserle humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells AT penelopeckayfedorov humancytomegalovirusul11proteininteractswiththereceptortyrosinephosphatasecd45resultinginfunctionalparalysisoftcells
_version_	1718424584332509184

The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.

Ejemplares similares