Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins

Autores
Mouna, Lina; Hernandez, Eva; Bonte, Dorine; Brost, Rebekka; Amazit, Larbi; Delgui, Laura Ruth; Brune, Wolfram; Geballe, Adam P.; Beau, Isabelle; Esclatine, Audrey
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Autophagy is activated early after human cytomegalovirus (HCMV) infection, but lateron the virus blocks autophagy. Here we characterized 2 HCMV proteins, TRS1 andIRS1, which inhibit autophagy during infection. Expression of either TRS1 or IRS1 wasable to block autophagy in different cell lines, independently of the EIF2S1 kinase,EIF2AK2/PKR. Instead, TRS1 and IRS1 interacted with the autophagy proteinBECN1/Beclin 1. We mapped the BECN1-binding domain (BBD) of IRS1 and TRS1 andfound it to be essential for autophagy inhibition. Mutant viruses that express only IRS1or TRS1 partially controlled autophagy, whereas a double mutant virus expressingneither protein stimulated autophagy. A mutant virus that did not express IRS1 andexpressed a truncated form of TRS1 in which the BBD was deleted, failed to controlautophagy. However, this mutant virus had similar replication kinetics as wild-type virus,suggesting that autophagy inhibition is not critical for viral replication. In fact, usingpharmacological modulators of autophagy and inhibition of autophagy by shRNAknockdown, we discovered that stimulating autophagy enhanced viral replication.Conversely, inhibiting autophagy decreased HCMV infection. Thus, our resultsdemonstrate a new proviral role of autophagy for a DNA virus
Fil: Mouna, Lina. Université Paris Sud; Francia
Fil: Hernandez, Eva. Université Paris Sud; Francia
Fil: Bonte, Dorine. Centre National de la Recherche Scientifique; Francia
Fil: Brost, Rebekka. Heinrich Pette Institute; Alemania
Fil: Amazit, Larbi. Université Paris Sud; Francia
Fil: Delgui, Laura Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Brune, Wolfram. Heinrich Pette Institute; Alemania
Fil: Geballe, Adam P.. University of Washington; Estados Unidos
Fil: Beau, Isabelle. Université Paris Sud; Francia
Fil: Esclatine, Audrey. Université Paris Sud; Francia
Materia
Autophagy
Becn1
Cytomegalovirus
Eif2ak2/Pkr
Irs1
Trs1
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:11336/41469
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/41469
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteinsMouna, LinaHernandez, EvaBonte, DorineBrost, RebekkaAmazit, LarbiDelgui, Laura RuthBrune, WolframGeballe, Adam P.Beau, IsabelleEsclatine, AudreyAutophagyBecn1CytomegalovirusEif2ak2/PkrIrs1Trs1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Autophagy is activated early after human cytomegalovirus (HCMV) infection, but lateron the virus blocks autophagy. Here we characterized 2 HCMV proteins, TRS1 andIRS1, which inhibit autophagy during infection. Expression of either TRS1 or IRS1 wasable to block autophagy in different cell lines, independently of the EIF2S1 kinase,EIF2AK2/PKR. Instead, TRS1 and IRS1 interacted with the autophagy proteinBECN1/Beclin 1. We mapped the BECN1-binding domain (BBD) of IRS1 and TRS1 andfound it to be essential for autophagy inhibition. Mutant viruses that express only IRS1or TRS1 partially controlled autophagy, whereas a double mutant virus expressingneither protein stimulated autophagy. A mutant virus that did not express IRS1 andexpressed a truncated form of TRS1 in which the BBD was deleted, failed to controlautophagy. However, this mutant virus had similar replication kinetics as wild-type virus,suggesting that autophagy inhibition is not critical for viral replication. In fact, usingpharmacological modulators of autophagy and inhibition of autophagy by shRNAknockdown, we discovered that stimulating autophagy enhanced viral replication.Conversely, inhibiting autophagy decreased HCMV infection. Thus, our resultsdemonstrate a new proviral role of autophagy for a DNA virusFil: Mouna, Lina. Université Paris Sud; FranciaFil: Hernandez, Eva. Université Paris Sud; FranciaFil: Bonte, Dorine. Centre National de la Recherche Scientifique; FranciaFil: Brost, Rebekka. Heinrich Pette Institute; AlemaniaFil: Amazit, Larbi. Université Paris Sud; FranciaFil: Delgui, Laura Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Brune, Wolfram. Heinrich Pette Institute; AlemaniaFil: Geballe, Adam P.. University of Washington; Estados UnidosFil: Beau, Isabelle. Université Paris Sud; FranciaFil: Esclatine, Audrey. Université Paris Sud; FranciaLandes Bioscience2015-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/41469Mouna, Lina; Hernandez, Eva; Bonte, Dorine; Brost, Rebekka; Amazit, Larbi; et al.; Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins; Landes Bioscience; Autophagy; 12; 2; 12-2015; 327-3421554-8627CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1080/15548627.2015.1125071info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/15548627.2015.1125071info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:13:06Zoai:ri.conicet.gov.ar:11336/41469instacron: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:34982025-10-22 11:13:06.621CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins
title Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins
spellingShingle Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins
Mouna, Lina
Autophagy
Becn1
Cytomegalovirus
Eif2ak2/Pkr
Irs1
Trs1
title_short Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins
title_full Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins
title_fullStr Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins
title_full_unstemmed Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins
title_sort Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins
dc.creator.none.fl_str_mv Mouna, Lina
Hernandez, Eva
Bonte, Dorine
Brost, Rebekka
Amazit, Larbi
Delgui, Laura Ruth
Brune, Wolfram
Geballe, Adam P.
Beau, Isabelle
Esclatine, Audrey
author Mouna, Lina
author_facet Mouna, Lina
Hernandez, Eva
Bonte, Dorine
Brost, Rebekka
Amazit, Larbi
Delgui, Laura Ruth
Brune, Wolfram
Geballe, Adam P.
Beau, Isabelle
Esclatine, Audrey
author_role author
author2 Hernandez, Eva
Bonte, Dorine
Brost, Rebekka
Amazit, Larbi
Delgui, Laura Ruth
Brune, Wolfram
Geballe, Adam P.
Beau, Isabelle
Esclatine, Audrey
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Autophagy
Becn1
Cytomegalovirus
Eif2ak2/Pkr
Irs1
Trs1
topic Autophagy
Becn1
Cytomegalovirus
Eif2ak2/Pkr
Irs1
Trs1
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Autophagy is activated early after human cytomegalovirus (HCMV) infection, but lateron the virus blocks autophagy. Here we characterized 2 HCMV proteins, TRS1 andIRS1, which inhibit autophagy during infection. Expression of either TRS1 or IRS1 wasable to block autophagy in different cell lines, independently of the EIF2S1 kinase,EIF2AK2/PKR. Instead, TRS1 and IRS1 interacted with the autophagy proteinBECN1/Beclin 1. We mapped the BECN1-binding domain (BBD) of IRS1 and TRS1 andfound it to be essential for autophagy inhibition. Mutant viruses that express only IRS1or TRS1 partially controlled autophagy, whereas a double mutant virus expressingneither protein stimulated autophagy. A mutant virus that did not express IRS1 andexpressed a truncated form of TRS1 in which the BBD was deleted, failed to controlautophagy. However, this mutant virus had similar replication kinetics as wild-type virus,suggesting that autophagy inhibition is not critical for viral replication. In fact, usingpharmacological modulators of autophagy and inhibition of autophagy by shRNAknockdown, we discovered that stimulating autophagy enhanced viral replication.Conversely, inhibiting autophagy decreased HCMV infection. Thus, our resultsdemonstrate a new proviral role of autophagy for a DNA virus
Fil: Mouna, Lina. Université Paris Sud; Francia
Fil: Hernandez, Eva. Université Paris Sud; Francia
Fil: Bonte, Dorine. Centre National de la Recherche Scientifique; Francia
Fil: Brost, Rebekka. Heinrich Pette Institute; Alemania
Fil: Amazit, Larbi. Université Paris Sud; Francia
Fil: Delgui, Laura Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Brune, Wolfram. Heinrich Pette Institute; Alemania
Fil: Geballe, Adam P.. University of Washington; Estados Unidos
Fil: Beau, Isabelle. Université Paris Sud; Francia
Fil: Esclatine, Audrey. Université Paris Sud; Francia
description Autophagy is activated early after human cytomegalovirus (HCMV) infection, but lateron the virus blocks autophagy. Here we characterized 2 HCMV proteins, TRS1 andIRS1, which inhibit autophagy during infection. Expression of either TRS1 or IRS1 wasable to block autophagy in different cell lines, independently of the EIF2S1 kinase,EIF2AK2/PKR. Instead, TRS1 and IRS1 interacted with the autophagy proteinBECN1/Beclin 1. We mapped the BECN1-binding domain (BBD) of IRS1 and TRS1 andfound it to be essential for autophagy inhibition. Mutant viruses that express only IRS1or TRS1 partially controlled autophagy, whereas a double mutant virus expressingneither protein stimulated autophagy. A mutant virus that did not express IRS1 andexpressed a truncated form of TRS1 in which the BBD was deleted, failed to controlautophagy. However, this mutant virus had similar replication kinetics as wild-type virus,suggesting that autophagy inhibition is not critical for viral replication. In fact, usingpharmacological modulators of autophagy and inhibition of autophagy by shRNAknockdown, we discovered that stimulating autophagy enhanced viral replication.Conversely, inhibiting autophagy decreased HCMV infection. Thus, our resultsdemonstrate a new proviral role of autophagy for a DNA virus
publishDate 2015
dc.date.none.fl_str_mv 2015-12
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/11336/41469
Mouna, Lina; Hernandez, Eva; Bonte, Dorine; Brost, Rebekka; Amazit, Larbi; et al.; Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins; Landes Bioscience; Autophagy; 12; 2; 12-2015; 327-342
1554-8627
CONICET Digital
CONICET
url http://hdl.handle.net/11336/41469
identifier_str_mv Mouna, Lina; Hernandez, Eva; Bonte, Dorine; Brost, Rebekka; Amazit, Larbi; et al.; Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins; Landes Bioscience; Autophagy; 12; 2; 12-2015; 327-342
1554-8627
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1080/15548627.2015.1125071
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/15548627.2015.1125071
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
application/pdf
dc.publisher.none.fl_str_mv Landes Bioscience
publisher.none.fl_str_mv Landes Bioscience
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
_version_ 1846781534049140736
score 12.982451

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