High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Med...

Autores
Poirson, Juline; Suarez, Irina Paula; Straub, Marie Laure; Cousido Siah, Alexandra; Peixoto, Paul; Hervouet, Eric; Foster, Anne; Mitschler, Andre; Mukobo, Noella; Chebaro, Yassmine; Garcin, Dominique; Recberlik, Sevda; Gaiddon, Christian; Altschuh, Daniele; Nomine, Yves; Podjarny, Alberto Daniel; Trave, Gilles; Masson, Murielle
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Persistent infection with some mucosal a-genus human papillomaviruses (HPVs; the most prevalent one being HPV16) can induce cervical carcinoma, anogenital cancers, and a subset of head and neck squamous cell carcinoma (HNSCC). Cutaneous β-genus HPVs (such as HPV5 and HPV8) associate with skin lesions that can progress into squamous cell carcinoma with sun exposure in Epidermodysplasia verruciformis patients and immunosuppressed patients. Here, we analyzed mechanisms used by E6 proteins from the a- and β-genus to inhibit the interferon-b (IFNB1) response. HPV16 E6 mediates this effect by a strong direct interaction with interferon regulatory factor 3 (IRF3). The binding site of E6 was localized within a flexible linker between the DNAbinding domain and the IRF-activation domain of IRF3 containing an LxxLL motif. The crystallographic structure of the complex between HPV16 E6 and the LxxLL motif of IRF3 was solved and compared with the structure of HPV16 E6 interacting with the LxxLL motif of the ubiquitin ligase E6AP. In contrast, cutaneous HPV5 and HPV8 E6 proteins bind to the IRF3-binding domain (IBiD) of the CREβ-binding protein (CBP), a key transcriptional coactivator in IRF3-mediated IFN-b expression.
Fil: Poirson, Juline. Université de Strasbourg; Francia
Fil: Suarez, Irina Paula. Université de Strasbourg; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Straub, Marie Laure. Université de Strasbourg; Francia
Fil: Cousido Siah, Alexandra. Université de Strasbourg; Francia
Fil: Peixoto, Paul. Inserm; Francia
Fil: Hervouet, Eric. Inserm; Francia
Fil: Foster, Anne. Université de Strasbourg; Francia
Fil: Mitschler, Andre. Université de Strasbourg; Francia
Fil: Mukobo, Noella. Université de Strasbourg; Francia
Fil: Chebaro, Yassmine. Université de Strasbourg; Francia
Fil: Garcin, Dominique. Universite Ifm Geneve (ifm); Suiza
Fil: Recberlik, Sevda. Inserm; Francia
Fil: Gaiddon, Christian. Inserm; Francia
Fil: Altschuh, Daniele. Université de Strasbourg; Francia
Fil: Nomine, Yves. Université de Strasbourg; Francia
Fil: Podjarny, Alberto Daniel. Université de Strasbourg; Francia
Fil: Trave, Gilles. Université de Strasbourg; Francia
Fil: Masson, Murielle. Université de Strasbourg; Francia
Materia
HPV
INTERACTOMIC
INTERFERONS
IRF3
THREE-DIMENSIONAL STRUCTURE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/214484
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/214484
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon ExpressionPoirson, JulineSuarez, Irina PaulaStraub, Marie LaureCousido Siah, AlexandraPeixoto, PaulHervouet, EricFoster, AnneMitschler, AndreMukobo, NoellaChebaro, YassmineGarcin, DominiqueRecberlik, SevdaGaiddon, ChristianAltschuh, DanieleNomine, YvesPodjarny, Alberto DanielTrave, GillesMasson, MurielleHPVINTERACTOMICINTERFERONSIRF3THREE-DIMENSIONAL STRUCTUREhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Persistent infection with some mucosal a-genus human papillomaviruses (HPVs; the most prevalent one being HPV16) can induce cervical carcinoma, anogenital cancers, and a subset of head and neck squamous cell carcinoma (HNSCC). Cutaneous β-genus HPVs (such as HPV5 and HPV8) associate with skin lesions that can progress into squamous cell carcinoma with sun exposure in Epidermodysplasia verruciformis patients and immunosuppressed patients. Here, we analyzed mechanisms used by E6 proteins from the a- and β-genus to inhibit the interferon-b (IFNB1) response. HPV16 E6 mediates this effect by a strong direct interaction with interferon regulatory factor 3 (IRF3). The binding site of E6 was localized within a flexible linker between the DNAbinding domain and the IRF-activation domain of IRF3 containing an LxxLL motif. The crystallographic structure of the complex between HPV16 E6 and the LxxLL motif of IRF3 was solved and compared with the structure of HPV16 E6 interacting with the LxxLL motif of the ubiquitin ligase E6AP. In contrast, cutaneous HPV5 and HPV8 E6 proteins bind to the IRF3-binding domain (IBiD) of the CREβ-binding protein (CBP), a key transcriptional coactivator in IRF3-mediated IFN-b expression.Fil: Poirson, Juline. Université de Strasbourg; FranciaFil: Suarez, Irina Paula. Université de Strasbourg; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Straub, Marie Laure. Université de Strasbourg; FranciaFil: Cousido Siah, Alexandra. Université de Strasbourg; FranciaFil: Peixoto, Paul. Inserm; FranciaFil: Hervouet, Eric. Inserm; FranciaFil: Foster, Anne. Université de Strasbourg; FranciaFil: Mitschler, Andre. Université de Strasbourg; FranciaFil: Mukobo, Noella. Université de Strasbourg; FranciaFil: Chebaro, Yassmine. Université de Strasbourg; FranciaFil: Garcin, Dominique. Universite Ifm Geneve (ifm); SuizaFil: Recberlik, Sevda. Inserm; FranciaFil: Gaiddon, Christian. Inserm; FranciaFil: Altschuh, Daniele. Université de Strasbourg; FranciaFil: Nomine, Yves. Université de Strasbourg; FranciaFil: Podjarny, Alberto Daniel. Université de Strasbourg; FranciaFil: Trave, Gilles. Université de Strasbourg; FranciaFil: Masson, Murielle. Université de Strasbourg; FranciaAmerican Society for Microbiology2022-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/214484Poirson, Juline; Suarez, Irina Paula; Straub, Marie Laure; Cousido Siah, Alexandra; Peixoto, Paul; et al.; High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression; American Society for Microbiology; Journal of Virology; 96; 10; 5-2022; 1-190022-538XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/jvi.01875-21info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:08Zoai:ri.conicet.gov.ar:11336/214484instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:01:09.177CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression
title High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression
spellingShingle High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression
Poirson, Juline
HPV
INTERACTOMIC
INTERFERONS
IRF3
THREE-DIMENSIONAL STRUCTURE
title_short High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression
title_full High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression
title_fullStr High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression
title_full_unstemmed High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression
title_sort High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression
dc.creator.none.fl_str_mv Poirson, Juline
Suarez, Irina Paula
Straub, Marie Laure
Cousido Siah, Alexandra
Peixoto, Paul
Hervouet, Eric
Foster, Anne
Mitschler, Andre
Mukobo, Noella
Chebaro, Yassmine
Garcin, Dominique
Recberlik, Sevda
Gaiddon, Christian
Altschuh, Daniele
Nomine, Yves
Podjarny, Alberto Daniel
Trave, Gilles
Masson, Murielle
author Poirson, Juline
author_facet Poirson, Juline
Suarez, Irina Paula
Straub, Marie Laure
Cousido Siah, Alexandra
Peixoto, Paul
Hervouet, Eric
Foster, Anne
Mitschler, Andre
Mukobo, Noella
Chebaro, Yassmine
Garcin, Dominique
Recberlik, Sevda
Gaiddon, Christian
Altschuh, Daniele
Nomine, Yves
Podjarny, Alberto Daniel
Trave, Gilles
Masson, Murielle
author_role author
author2 Suarez, Irina Paula
Straub, Marie Laure
Cousido Siah, Alexandra
Peixoto, Paul
Hervouet, Eric
Foster, Anne
Mitschler, Andre
Mukobo, Noella
Chebaro, Yassmine
Garcin, Dominique
Recberlik, Sevda
Gaiddon, Christian
Altschuh, Daniele
Nomine, Yves
Podjarny, Alberto Daniel
Trave, Gilles
Masson, Murielle
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HPV
INTERACTOMIC
INTERFERONS
IRF3
THREE-DIMENSIONAL STRUCTURE
topic HPV
INTERACTOMIC
INTERFERONS
IRF3
THREE-DIMENSIONAL STRUCTURE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Persistent infection with some mucosal a-genus human papillomaviruses (HPVs; the most prevalent one being HPV16) can induce cervical carcinoma, anogenital cancers, and a subset of head and neck squamous cell carcinoma (HNSCC). Cutaneous β-genus HPVs (such as HPV5 and HPV8) associate with skin lesions that can progress into squamous cell carcinoma with sun exposure in Epidermodysplasia verruciformis patients and immunosuppressed patients. Here, we analyzed mechanisms used by E6 proteins from the a- and β-genus to inhibit the interferon-b (IFNB1) response. HPV16 E6 mediates this effect by a strong direct interaction with interferon regulatory factor 3 (IRF3). The binding site of E6 was localized within a flexible linker between the DNAbinding domain and the IRF-activation domain of IRF3 containing an LxxLL motif. The crystallographic structure of the complex between HPV16 E6 and the LxxLL motif of IRF3 was solved and compared with the structure of HPV16 E6 interacting with the LxxLL motif of the ubiquitin ligase E6AP. In contrast, cutaneous HPV5 and HPV8 E6 proteins bind to the IRF3-binding domain (IBiD) of the CREβ-binding protein (CBP), a key transcriptional coactivator in IRF3-mediated IFN-b expression.
Fil: Poirson, Juline. Université de Strasbourg; Francia
Fil: Suarez, Irina Paula. Université de Strasbourg; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Straub, Marie Laure. Université de Strasbourg; Francia
Fil: Cousido Siah, Alexandra. Université de Strasbourg; Francia
Fil: Peixoto, Paul. Inserm; Francia
Fil: Hervouet, Eric. Inserm; Francia
Fil: Foster, Anne. Université de Strasbourg; Francia
Fil: Mitschler, Andre. Université de Strasbourg; Francia
Fil: Mukobo, Noella. Université de Strasbourg; Francia
Fil: Chebaro, Yassmine. Université de Strasbourg; Francia
Fil: Garcin, Dominique. Universite Ifm Geneve (ifm); Suiza
Fil: Recberlik, Sevda. Inserm; Francia
Fil: Gaiddon, Christian. Inserm; Francia
Fil: Altschuh, Daniele. Université de Strasbourg; Francia
Fil: Nomine, Yves. Université de Strasbourg; Francia
Fil: Podjarny, Alberto Daniel. Université de Strasbourg; Francia
Fil: Trave, Gilles. Université de Strasbourg; Francia
Fil: Masson, Murielle. Université de Strasbourg; Francia
description Persistent infection with some mucosal a-genus human papillomaviruses (HPVs; the most prevalent one being HPV16) can induce cervical carcinoma, anogenital cancers, and a subset of head and neck squamous cell carcinoma (HNSCC). Cutaneous β-genus HPVs (such as HPV5 and HPV8) associate with skin lesions that can progress into squamous cell carcinoma with sun exposure in Epidermodysplasia verruciformis patients and immunosuppressed patients. Here, we analyzed mechanisms used by E6 proteins from the a- and β-genus to inhibit the interferon-b (IFNB1) response. HPV16 E6 mediates this effect by a strong direct interaction with interferon regulatory factor 3 (IRF3). The binding site of E6 was localized within a flexible linker between the DNAbinding domain and the IRF-activation domain of IRF3 containing an LxxLL motif. The crystallographic structure of the complex between HPV16 E6 and the LxxLL motif of IRF3 was solved and compared with the structure of HPV16 E6 interacting with the LxxLL motif of the ubiquitin ligase E6AP. In contrast, cutaneous HPV5 and HPV8 E6 proteins bind to the IRF3-binding domain (IBiD) of the CREβ-binding protein (CBP), a key transcriptional coactivator in IRF3-mediated IFN-b expression.
publishDate 2022
dc.date.none.fl_str_mv 2022-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/214484
Poirson, Juline; Suarez, Irina Paula; Straub, Marie Laure; Cousido Siah, Alexandra; Peixoto, Paul; et al.; High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression; American Society for Microbiology; Journal of Virology; 96; 10; 5-2022; 1-19
0022-538X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/214484
identifier_str_mv Poirson, Juline; Suarez, Irina Paula; Straub, Marie Laure; Cousido Siah, Alexandra; Peixoto, Paul; et al.; High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression; American Society for Microbiology; Journal of Virology; 96; 10; 5-2022; 1-19
0022-538X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/jvi.01875-21
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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