Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells

Autores
Ojeda, Diego Sebastian; Grasso, Daniel Hector; Urquiza, Javier Mariano; Till, Andreas; Vaccaro, Maria Ines; Quarleri, Jorge Fabian
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Despite more than 30 years of extensive research efforts, a complete understanding of the neurological consequences of HIV central nervous system (CNS) infection remains elusive. HIV is not only able to establish a viral reservoir in the CNS but also to initiate manifestation of neurodegenerative diseases. These neurological disorders may arise because of virus-induced activation of the inflammasome in CNS cells, including astrocytes. Nevertheless, in some productive viral infection scenarios, selective autophagy may reduce inflammation through mitochondrial degradation ("mitophagy") to counteract inflammasome activation. In this study, using cultured human astrocytes, we demonstrate that-depending on the HIV infection outcome-cells may resist death, or succumb by inflammasome activation when viral infection is productive or abortive, respectively. Cells productively infected with HIV were able to attenuate both mitochondrial ROS production and mitochondrial membrane potential dissipation, thus exhibiting cell death resistance. Interestingly, mitochondrial injury was counteracted by increasing the autophagic flux and by activating mitophagy. Conversely, astrocytes exposed to HIV in an abortive scenario showed prominent mitochondrial damage, inflammasome activation, and cell death. This bystander effect occurred after cell-to-cell contact with HIV-productively infected astrocytes. In summary, we demonstrate a tight functional crosstalk between viral infection mode, inflammasome activation, autophagy pathways and cell fate in the context of HIV infection. Moreover, mitophagy is crucial for cell death resistance in HIV-productively infected astrocytes, but its impairment may favor inflammasome-mediated cell death in abortively infected cells.
Fil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Grasso, Daniel Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Urquiza, Javier Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Till, Andreas. Universitat Bonn; Alemania
Fil: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Materia
ASTROCYTES
AUTOPHAGY
CENTRAL NERVOUS SYSTEM
HIV
INFLAMMASOME
MITOCHONDRIA
MITOPHAGY
RESERVOIRS
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:11336/88339
Acceder
id CONICETDig_db374395fcbae6ef49b085a59373551c
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cellsOjeda, Diego SebastianGrasso, Daniel HectorUrquiza, Javier MarianoTill, AndreasVaccaro, Maria InesQuarleri, Jorge FabianASTROCYTESAUTOPHAGYCENTRAL NERVOUS SYSTEMHIVINFLAMMASOMEMITOCHONDRIAMITOPHAGYRESERVOIRShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Despite more than 30 years of extensive research efforts, a complete understanding of the neurological consequences of HIV central nervous system (CNS) infection remains elusive. HIV is not only able to establish a viral reservoir in the CNS but also to initiate manifestation of neurodegenerative diseases. These neurological disorders may arise because of virus-induced activation of the inflammasome in CNS cells, including astrocytes. Nevertheless, in some productive viral infection scenarios, selective autophagy may reduce inflammation through mitochondrial degradation ("mitophagy") to counteract inflammasome activation. In this study, using cultured human astrocytes, we demonstrate that-depending on the HIV infection outcome-cells may resist death, or succumb by inflammasome activation when viral infection is productive or abortive, respectively. Cells productively infected with HIV were able to attenuate both mitochondrial ROS production and mitochondrial membrane potential dissipation, thus exhibiting cell death resistance. Interestingly, mitochondrial injury was counteracted by increasing the autophagic flux and by activating mitophagy. Conversely, astrocytes exposed to HIV in an abortive scenario showed prominent mitochondrial damage, inflammasome activation, and cell death. This bystander effect occurred after cell-to-cell contact with HIV-productively infected astrocytes. In summary, we demonstrate a tight functional crosstalk between viral infection mode, inflammasome activation, autophagy pathways and cell fate in the context of HIV infection. Moreover, mitophagy is crucial for cell death resistance in HIV-productively infected astrocytes, but its impairment may favor inflammasome-mediated cell death in abortively infected cells.Fil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Grasso, Daniel Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Urquiza, Javier Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Till, Andreas. Universitat Bonn; AlemaniaFil: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFrontiers Media SA2018-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/88339Ojeda, Diego Sebastian; Grasso, Daniel Hector; Urquiza, Javier Mariano; Till, Andreas; Vaccaro, Maria Ines; et al.; Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells; Frontiers Media SA; Frontiers in Immunology; 9; 2633; 11-2018; 1-191664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2018.02633/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02633info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:07:39Zoai:ri.conicet.gov.ar:11336/88339instacron: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:34982025-09-10 13:07:39.826CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells
title Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells
spellingShingle Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells
Ojeda, Diego Sebastian
ASTROCYTES
AUTOPHAGY
CENTRAL NERVOUS SYSTEM
HIV
INFLAMMASOME
MITOCHONDRIA
MITOPHAGY
RESERVOIRS
title_short Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells
title_full Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells
title_fullStr Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells
title_full_unstemmed Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells
title_sort Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells
dc.creator.none.fl_str_mv Ojeda, Diego Sebastian
Grasso, Daniel Hector
Urquiza, Javier Mariano
Till, Andreas
Vaccaro, Maria Ines
Quarleri, Jorge Fabian
author Ojeda, Diego Sebastian
author_facet Ojeda, Diego Sebastian
Grasso, Daniel Hector
Urquiza, Javier Mariano
Till, Andreas
Vaccaro, Maria Ines
Quarleri, Jorge Fabian
author_role author
author2 Grasso, Daniel Hector
Urquiza, Javier Mariano
Till, Andreas
Vaccaro, Maria Ines
Quarleri, Jorge Fabian
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ASTROCYTES
AUTOPHAGY
CENTRAL NERVOUS SYSTEM
HIV
INFLAMMASOME
MITOCHONDRIA
MITOPHAGY
RESERVOIRS
topic ASTROCYTES
AUTOPHAGY
CENTRAL NERVOUS SYSTEM
HIV
INFLAMMASOME
MITOCHONDRIA
MITOPHAGY
RESERVOIRS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Despite more than 30 years of extensive research efforts, a complete understanding of the neurological consequences of HIV central nervous system (CNS) infection remains elusive. HIV is not only able to establish a viral reservoir in the CNS but also to initiate manifestation of neurodegenerative diseases. These neurological disorders may arise because of virus-induced activation of the inflammasome in CNS cells, including astrocytes. Nevertheless, in some productive viral infection scenarios, selective autophagy may reduce inflammation through mitochondrial degradation ("mitophagy") to counteract inflammasome activation. In this study, using cultured human astrocytes, we demonstrate that-depending on the HIV infection outcome-cells may resist death, or succumb by inflammasome activation when viral infection is productive or abortive, respectively. Cells productively infected with HIV were able to attenuate both mitochondrial ROS production and mitochondrial membrane potential dissipation, thus exhibiting cell death resistance. Interestingly, mitochondrial injury was counteracted by increasing the autophagic flux and by activating mitophagy. Conversely, astrocytes exposed to HIV in an abortive scenario showed prominent mitochondrial damage, inflammasome activation, and cell death. This bystander effect occurred after cell-to-cell contact with HIV-productively infected astrocytes. In summary, we demonstrate a tight functional crosstalk between viral infection mode, inflammasome activation, autophagy pathways and cell fate in the context of HIV infection. Moreover, mitophagy is crucial for cell death resistance in HIV-productively infected astrocytes, but its impairment may favor inflammasome-mediated cell death in abortively infected cells.
Fil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Grasso, Daniel Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Urquiza, Javier Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Till, Andreas. Universitat Bonn; Alemania
Fil: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
description Despite more than 30 years of extensive research efforts, a complete understanding of the neurological consequences of HIV central nervous system (CNS) infection remains elusive. HIV is not only able to establish a viral reservoir in the CNS but also to initiate manifestation of neurodegenerative diseases. These neurological disorders may arise because of virus-induced activation of the inflammasome in CNS cells, including astrocytes. Nevertheless, in some productive viral infection scenarios, selective autophagy may reduce inflammation through mitochondrial degradation ("mitophagy") to counteract inflammasome activation. In this study, using cultured human astrocytes, we demonstrate that-depending on the HIV infection outcome-cells may resist death, or succumb by inflammasome activation when viral infection is productive or abortive, respectively. Cells productively infected with HIV were able to attenuate both mitochondrial ROS production and mitochondrial membrane potential dissipation, thus exhibiting cell death resistance. Interestingly, mitochondrial injury was counteracted by increasing the autophagic flux and by activating mitophagy. Conversely, astrocytes exposed to HIV in an abortive scenario showed prominent mitochondrial damage, inflammasome activation, and cell death. This bystander effect occurred after cell-to-cell contact with HIV-productively infected astrocytes. In summary, we demonstrate a tight functional crosstalk between viral infection mode, inflammasome activation, autophagy pathways and cell fate in the context of HIV infection. Moreover, mitophagy is crucial for cell death resistance in HIV-productively infected astrocytes, but its impairment may favor inflammasome-mediated cell death in abortively infected cells.
publishDate 2018
dc.date.none.fl_str_mv 2018-11
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/11336/88339
Ojeda, Diego Sebastian; Grasso, Daniel Hector; Urquiza, Javier Mariano; Till, Andreas; Vaccaro, Maria Ines; et al.; Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells; Frontiers Media SA; Frontiers in Immunology; 9; 2633; 11-2018; 1-19
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/88339
identifier_str_mv Ojeda, Diego Sebastian; Grasso, Daniel Hector; Urquiza, Javier Mariano; Till, Andreas; Vaccaro, Maria Ines; et al.; Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells; Frontiers Media SA; Frontiers in Immunology; 9; 2633; 11-2018; 1-19
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2018.02633/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02633
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
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 12.993085

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