Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.7/930 |
Resumo: | Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1CIM to the T. gondii virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American T. gondii strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1CIM, indicating co-adaptation of host cell resistance GTPases and T. gondii virulence effectors. |
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Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived miceAnimalsDisease ResistanceFemaleFibroblastsGTP PhosphohydrolasesHEK293 CellsHost-Parasite InteractionsHumansMaleMiceMice, Inbred C57BLProtein IsoformsProtozoan ProteinsSelection, GeneticToxoplasmaToxoplasmosis, AnimalVirulenceSome strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1CIM to the T. gondii virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American T. gondii strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1CIM, indicating co-adaptation of host cell resistance GTPases and T. gondii virulence effectors.ARCAMurillo-León, MateoMüller, Urs BZimmermann, InesSingh, ShishirWiddershooven, PiaCampos, CláudiaAlvarez, CatalinaKönen-Waisman, StephanieLukes, NahleenRuzsics, ZsoltHoward, Jonathan CSchwemmle, MartinSteinfeldt, Tobias2020-03-11T10:44:22Z2019-03-152019-03-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.7/930engMurillo-León M, Müller UB, Zimmermann I, et al. Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice [published correction appears in Nat Commun. 2019 Apr 4;10(1):1645]. Nat Commun. 2019;10(1):1233. Published 2019 Mar 1510.1038/s41467-019-09200-2info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-29T14:35:20Zoai:arca.igc.gulbenkian.pt:10400.7/930Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:12:07.942249Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice |
title |
Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice |
spellingShingle |
Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice Murillo-León, Mateo Animals Disease Resistance Female Fibroblasts GTP Phosphohydrolases HEK293 Cells Host-Parasite Interactions Humans Male Mice Mice, Inbred C57BL Protein Isoforms Protozoan Proteins Selection, Genetic Toxoplasma Toxoplasmosis, Animal Virulence |
title_short |
Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice |
title_full |
Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice |
title_fullStr |
Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice |
title_full_unstemmed |
Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice |
title_sort |
Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice |
author |
Murillo-León, Mateo |
author_facet |
Murillo-León, Mateo Müller, Urs B Zimmermann, Ines Singh, Shishir Widdershooven, Pia Campos, Cláudia Alvarez, Catalina Könen-Waisman, Stephanie Lukes, Nahleen Ruzsics, Zsolt Howard, Jonathan C Schwemmle, Martin Steinfeldt, Tobias |
author_role |
author |
author2 |
Müller, Urs B Zimmermann, Ines Singh, Shishir Widdershooven, Pia Campos, Cláudia Alvarez, Catalina Könen-Waisman, Stephanie Lukes, Nahleen Ruzsics, Zsolt Howard, Jonathan C Schwemmle, Martin Steinfeldt, Tobias |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
ARCA |
dc.contributor.author.fl_str_mv |
Murillo-León, Mateo Müller, Urs B Zimmermann, Ines Singh, Shishir Widdershooven, Pia Campos, Cláudia Alvarez, Catalina Könen-Waisman, Stephanie Lukes, Nahleen Ruzsics, Zsolt Howard, Jonathan C Schwemmle, Martin Steinfeldt, Tobias |
dc.subject.por.fl_str_mv |
Animals Disease Resistance Female Fibroblasts GTP Phosphohydrolases HEK293 Cells Host-Parasite Interactions Humans Male Mice Mice, Inbred C57BL Protein Isoforms Protozoan Proteins Selection, Genetic Toxoplasma Toxoplasmosis, Animal Virulence |
topic |
Animals Disease Resistance Female Fibroblasts GTP Phosphohydrolases HEK293 Cells Host-Parasite Interactions Humans Male Mice Mice, Inbred C57BL Protein Isoforms Protozoan Proteins Selection, Genetic Toxoplasma Toxoplasmosis, Animal Virulence |
description |
Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1CIM to the T. gondii virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American T. gondii strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1CIM, indicating co-adaptation of host cell resistance GTPases and T. gondii virulence effectors. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-03-15 2019-03-15T00:00:00Z 2020-03-11T10:44:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.7/930 |
url |
http://hdl.handle.net/10400.7/930 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Murillo-León M, Müller UB, Zimmermann I, et al. Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice [published correction appears in Nat Commun. 2019 Apr 4;10(1):1645]. Nat Commun. 2019;10(1):1233. Published 2019 Mar 15 10.1038/s41467-019-09200-2 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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