Discovery of the first PD-1 ligand encoded by a pathogen

Large double-stranded DNA viruses deploy multiple strategies to subvert host immune defenses. Some of these tactics are mediated by viral gene products acquired by horizontal gene transfer from the corresponding hosts and shaped throughout evolution. The programmed death-1 (PD-1) receptor and its li...

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Detalles Bibliográficos
Autores: Martínez Vicente, Pablo, Poblador Bonet, Francesc, Leitner, Judith, Farré Marimon, Domènec, Steinberger, Peter, Engel Rocamora, Pablo, Angulo Aguado, Ana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/221875
Acceso en línea:https://hdl.handle.net/2445/221875
Access Level:acceso abierto
Palabra clave:Lligands (Bioquímica)
Mort cel·lular
Immunologia
Herpesvirus
Ligands (Biochemistry)
Cell death
Immunology
Herpesviruses
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spelling Discovery of the first PD-1 ligand encoded by a pathogenMartínez Vicente, PabloPoblador Bonet, FrancescLeitner, JudithFarré Marimon, DomènecSteinberger, PeterEngel Rocamora, PabloAngulo Aguado, AnaLligands (Bioquímica)Mort cel·lularImmunologiaHerpesvirusLigands (Biochemistry)Cell deathImmunologyHerpesvirusesLarge double-stranded DNA viruses deploy multiple strategies to subvert host immune defenses. Some of these tactics are mediated by viral gene products acquired by horizontal gene transfer from the corresponding hosts and shaped throughout evolution. The programmed death-1 (PD-1) receptor and its ligands, PD-L1 and PD-L2, play a pivotal role attenuating T-cell responses and regulating immune tolerance. In this study, we report the first functional PD-L1 homolog gene (De2) found in a pathogen. De2, captured by a gherpesvirus from its host during co-evolution around 50 million years ago, encodes a cell-surface glycoprotein that interacts with high affinity and stability with host PD-1. We also find that mutations evolved by the viral protein result in a significant loss of its ability to interact in cis with CD80, an interaction that for PD-L1:CD80 has been reported to block PD-1 inhibitory pathways. Furthermore, we demonstrate that the viral protein strongly inhibits T-cell signaling. Our observations suggest that PD-L1 homologs may enable viruses to evade T cell responses, favor their replication, and prevent excessive tissue damage. Altogether, our findings reveal a novel viral immunosuppressive strategy and highlight the importance of the modulation of the PD-1/PD-L1 axis during viral infections.Frontiers Media2025202520222025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/221875Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.1007334Frontiers in Immunology, 2022, vol. 13https://doi.org/10.3389/fimmu.2022.1007334cc-by (c) Martínez Vicente, Pablo et al., 2022http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2218752026-05-29T05:05:01Z
dc.title.none.fl_str_mv Discovery of the first PD-1 ligand encoded by a pathogen
title Discovery of the first PD-1 ligand encoded by a pathogen
spellingShingle Discovery of the first PD-1 ligand encoded by a pathogen
Martínez Vicente, Pablo
Lligands (Bioquímica)
Mort cel·lular
Immunologia
Herpesvirus
Ligands (Biochemistry)
Cell death
Immunology
Herpesviruses
title_short Discovery of the first PD-1 ligand encoded by a pathogen
title_full Discovery of the first PD-1 ligand encoded by a pathogen
title_fullStr Discovery of the first PD-1 ligand encoded by a pathogen
title_full_unstemmed Discovery of the first PD-1 ligand encoded by a pathogen
title_sort Discovery of the first PD-1 ligand encoded by a pathogen
dc.creator.none.fl_str_mv Martínez Vicente, Pablo
Poblador Bonet, Francesc
Leitner, Judith
Farré Marimon, Domènec
Steinberger, Peter
Engel Rocamora, Pablo
Angulo Aguado, Ana
author Martínez Vicente, Pablo
author_facet Martínez Vicente, Pablo
Poblador Bonet, Francesc
Leitner, Judith
Farré Marimon, Domènec
Steinberger, Peter
Engel Rocamora, Pablo
Angulo Aguado, Ana
author_role author
author2 Poblador Bonet, Francesc
Leitner, Judith
Farré Marimon, Domènec
Steinberger, Peter
Engel Rocamora, Pablo
Angulo Aguado, Ana
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Lligands (Bioquímica)
Mort cel·lular
Immunologia
Herpesvirus
Ligands (Biochemistry)
Cell death
Immunology
Herpesviruses
topic Lligands (Bioquímica)
Mort cel·lular
Immunologia
Herpesvirus
Ligands (Biochemistry)
Cell death
Immunology
Herpesviruses
description Large double-stranded DNA viruses deploy multiple strategies to subvert host immune defenses. Some of these tactics are mediated by viral gene products acquired by horizontal gene transfer from the corresponding hosts and shaped throughout evolution. The programmed death-1 (PD-1) receptor and its ligands, PD-L1 and PD-L2, play a pivotal role attenuating T-cell responses and regulating immune tolerance. In this study, we report the first functional PD-L1 homolog gene (De2) found in a pathogen. De2, captured by a gherpesvirus from its host during co-evolution around 50 million years ago, encodes a cell-surface glycoprotein that interacts with high affinity and stability with host PD-1. We also find that mutations evolved by the viral protein result in a significant loss of its ability to interact in cis with CD80, an interaction that for PD-L1:CD80 has been reported to block PD-1 inhibitory pathways. Furthermore, we demonstrate that the viral protein strongly inhibits T-cell signaling. Our observations suggest that PD-L1 homologs may enable viruses to evade T cell responses, favor their replication, and prevent excessive tissue damage. Altogether, our findings reveal a novel viral immunosuppressive strategy and highlight the importance of the modulation of the PD-1/PD-L1 axis during viral infections.
publishDate 2022
dc.date.none.fl_str_mv 2022
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/221875
url https://hdl.handle.net/2445/221875
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.1007334
Frontiers in Immunology, 2022, vol. 13
https://doi.org/10.3389/fimmu.2022.1007334
dc.rights.none.fl_str_mv cc-by (c) Martínez Vicente, Pablo et al., 2022
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Martínez Vicente, Pablo et al., 2022
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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