Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo

A complex link exists between HIV-1 and autophagy, and discordant results have been reported in different in vitro models regarding the way HIV and autophagy modulate each other. Despite this, there is very limited knowledge about the interplay between HIV and autophagy in vivo in lymphoid tissue, d...

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Autores: Pedreño-López, Sònia|||0000-0002-1919-3530, García Rodríguez, Elisabet, Guerrero, Dolores, Gomez, Elisabet|||0000-0002-9779-5940, Molina Mateu, Laura, Orera Pérez, Fernando, Senserrich, Jordi|||0000-0002-8021-1718, Clotet Sala, Bonaventura|||0000-0003-3232-4598, Cabrera Navarro, Cecilia|||0000-0002-9941-6828
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:282866
Acesso em linha:https://ddd.uab.cat/record/282866
https://dx.doi.org/urn:doi:10.1038/s41598-022-11181-0
Access Level:acceso abierto
Palavra-chave:HIV infections
Macroautophagy
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spelling Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivoPedreño-López, Sònia|||0000-0002-1919-3530García Rodríguez, ElisabetGuerrero, DoloresGomez, Elisabet|||0000-0002-9779-5940Molina Mateu, LauraOrera Pérez, FernandoSenserrich, Jordi|||0000-0002-8021-1718Clotet Sala, Bonaventura|||0000-0003-3232-4598Cabrera Navarro, Cecilia|||0000-0002-9941-6828HIV infectionsMacroautophagyA complex link exists between HIV-1 and autophagy, and discordant results have been reported in different in vitro models regarding the way HIV and autophagy modulate each other. Despite this, there is very limited knowledge about the interplay between HIV and autophagy in vivo in lymphoid tissue, due in part by the lack of cell models that recapitulate the in vivo setting. Here, we evaluate the interrelationship between HIV and autophagy using human ex vivo lymphoid tissue cultures as an HIV infection model. Our results showed that human lymphoid aggregated cultures (HLACs) from tonsillar tissue displayed fully functional autophagic activity. In this system, HIV infection resulted in an increase in autophagy. Notably, we observed that both, autophagy-enhancing (rapamycin) or blocking drugs (3-methyladenine, chloroquine and bafilomycin), were able to decrease HIV-DNA levels and HIV replication. Therefore, efficient HIV-1 replication requires a fine-tuned level of autophagy, so modifications of this balance will have a negative impact on its replication. Therefore, targeting the autophagic pathway could be a new therapeutic approach to be explored to treat HIV-1 infection. Ex vivo cultures of human lymphoid tissue are a suitable model to obtain further insights into HIV and its intricate relationship with autophagy.Universitat Autònoma de Barcelona. Departament de Cirurgia 22022-01-0120222022-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/282866https://dx.doi.org/urn:doi:10.1038/s41598-022-11181-0reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02408Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/01053Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/01226open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2828662026-06-06T12:50:31Z
dc.title.none.fl_str_mv Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo
title Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo
spellingShingle Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo
Pedreño-López, Sònia|||0000-0002-1919-3530
HIV infections
Macroautophagy
title_short Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo
title_full Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo
title_fullStr Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo
title_full_unstemmed Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo
title_sort Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo
dc.creator.none.fl_str_mv Pedreño-López, Sònia|||0000-0002-1919-3530
García Rodríguez, Elisabet
Guerrero, Dolores
Gomez, Elisabet|||0000-0002-9779-5940
Molina Mateu, Laura
Orera Pérez, Fernando
Senserrich, Jordi|||0000-0002-8021-1718
Clotet Sala, Bonaventura|||0000-0003-3232-4598
Cabrera Navarro, Cecilia|||0000-0002-9941-6828
author Pedreño-López, Sònia|||0000-0002-1919-3530
author_facet Pedreño-López, Sònia|||0000-0002-1919-3530
García Rodríguez, Elisabet
Guerrero, Dolores
Gomez, Elisabet|||0000-0002-9779-5940
Molina Mateu, Laura
Orera Pérez, Fernando
Senserrich, Jordi|||0000-0002-8021-1718
Clotet Sala, Bonaventura|||0000-0003-3232-4598
Cabrera Navarro, Cecilia|||0000-0002-9941-6828
author_role author
author2 García Rodríguez, Elisabet
Guerrero, Dolores
Gomez, Elisabet|||0000-0002-9779-5940
Molina Mateu, Laura
Orera Pérez, Fernando
Senserrich, Jordi|||0000-0002-8021-1718
Clotet Sala, Bonaventura|||0000-0003-3232-4598
Cabrera Navarro, Cecilia|||0000-0002-9941-6828
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Departament de Cirurgia
dc.subject.none.fl_str_mv HIV infections
Macroautophagy
topic HIV infections
Macroautophagy
description A complex link exists between HIV-1 and autophagy, and discordant results have been reported in different in vitro models regarding the way HIV and autophagy modulate each other. Despite this, there is very limited knowledge about the interplay between HIV and autophagy in vivo in lymphoid tissue, due in part by the lack of cell models that recapitulate the in vivo setting. Here, we evaluate the interrelationship between HIV and autophagy using human ex vivo lymphoid tissue cultures as an HIV infection model. Our results showed that human lymphoid aggregated cultures (HLACs) from tonsillar tissue displayed fully functional autophagic activity. In this system, HIV infection resulted in an increase in autophagy. Notably, we observed that both, autophagy-enhancing (rapamycin) or blocking drugs (3-methyladenine, chloroquine and bafilomycin), were able to decrease HIV-DNA levels and HIV replication. Therefore, efficient HIV-1 replication requires a fine-tuned level of autophagy, so modifications of this balance will have a negative impact on its replication. Therefore, targeting the autophagic pathway could be a new therapeutic approach to be explored to treat HIV-1 infection. Ex vivo cultures of human lymphoid tissue are a suitable model to obtain further insights into HIV and its intricate relationship with autophagy.
publishDate 2022
dc.date.none.fl_str_mv 2
2022-01-01
2022
2022-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/282866
https://dx.doi.org/urn:doi:10.1038/s41598-022-11181-0
url https://ddd.uab.cat/record/282866
https://dx.doi.org/urn:doi:10.1038/s41598-022-11181-0
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02408
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/01053
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/01226
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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