IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation
The persistence of latent HIV reservoirs allows for viral rebound upon antiretroviral therapy interruption, hindering effective HIV-1 cure. Emerging evidence suggests that modulation of innate immune stimulation could impact viral latency and contribute to the clearing of HIV reservoir. Here, the la...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:281812 |
| Acceso en línea: | https://ddd.uab.cat/record/281812 https://dx.doi.org/urn:doi:10.3389/fimmu.2022.1001068 |
| Access Level: | acceso abierto |
| Palabra clave: | HIV-1 cure strategies Innate immunity IRF7 JAK-STAT signalling Latency reversal agents |
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IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activationEzeonwumelu, I.J.|||0000-0003-4007-2212García Vidal, Edurne|||0000-0003-0698-8710Felip, Eudald|||0000-0002-3812-1313Puertas, Maria C.|||0000-0002-6750-2318Oriol-Tordera, Bruna|||0000-0002-2714-9097Gutiérrez-Chamorro, Lucía|||0000-0002-7649-951XGohr, AndréRuiz Riol, Marta|||0000-0003-1899-8879Massanella, Marta|||0000-0002-3326-151XClotet Sala, Bonaventura|||0000-0003-3232-4598Martínez Picado, Francisco Javier|||0000-0002-4916-2129Badia, Roger|||0000-0003-3982-7577Riveira Muñoz, Eva|||0000-0002-6396-1162Ballana, Ester|||0000-0002-5215-7363HIV-1 cure strategiesInnate immunityIRF7JAK-STAT signallingLatency reversal agentsThe persistence of latent HIV reservoirs allows for viral rebound upon antiretroviral therapy interruption, hindering effective HIV-1 cure. Emerging evidence suggests that modulation of innate immune stimulation could impact viral latency and contribute to the clearing of HIV reservoir. Here, the latency reactivation capacity of a subclass of selective JAK2 inhibitors was characterized as a potential novel therapeutic strategy for HIV-1 cure. Notably, JAK2 inhibitors reversed HIV-1 latency in non-clonal lymphoid and myeloid in vitro models of HIV-1 latency and also ex vivo in CD4+ T cells from ART+ PWH, albeit its function was not dependent on JAK2 expression. Immunophenotypic characterization and whole transcriptomic profiling supported reactivation data, showing common gene expression signatures between latency reactivating agents (LRA; JAK2i fedratinib and PMA) in contrast to other JAK inhibitors, but with significantly fewer affected gene sets in the pathway analysis. In depth evaluation of differentially expressed genes, identified a significant upregulation of IRF7 expression despite the blockade of the JAK-STAT pathway and downregulation of proinflammatory cytokines and chemokines. Moreover, IRF7 expression levels positively correlated with HIV latency reactivation capacity of JAK2 inhibitors and also other common LRAs. Collectively, these results represent a promising step towards HIV eradication by demonstrating the potential of innate immune modulation for reducing the viral reservoir through a novel pathway driven by IRF7.Universitat Autònoma de Barcelona 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/281812https://dx.doi.org/urn:doi:10.3389/fimmu.2022.1001068reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00194Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-109870RB-I00open 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:2818122026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation |
| title |
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation |
| spellingShingle |
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation Ezeonwumelu, I.J.|||0000-0003-4007-2212 HIV-1 cure strategies Innate immunity IRF7 JAK-STAT signalling Latency reversal agents |
| title_short |
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation |
| title_full |
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation |
| title_fullStr |
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation |
| title_full_unstemmed |
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation |
| title_sort |
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation |
| dc.creator.none.fl_str_mv |
Ezeonwumelu, I.J.|||0000-0003-4007-2212 García Vidal, Edurne|||0000-0003-0698-8710 Felip, Eudald|||0000-0002-3812-1313 Puertas, Maria C.|||0000-0002-6750-2318 Oriol-Tordera, Bruna|||0000-0002-2714-9097 Gutiérrez-Chamorro, Lucía|||0000-0002-7649-951X Gohr, André Ruiz Riol, Marta|||0000-0003-1899-8879 Massanella, Marta|||0000-0002-3326-151X Clotet Sala, Bonaventura|||0000-0003-3232-4598 Martínez Picado, Francisco Javier|||0000-0002-4916-2129 Badia, Roger|||0000-0003-3982-7577 Riveira Muñoz, Eva|||0000-0002-6396-1162 Ballana, Ester|||0000-0002-5215-7363 |
| author |
Ezeonwumelu, I.J.|||0000-0003-4007-2212 |
| author_facet |
Ezeonwumelu, I.J.|||0000-0003-4007-2212 García Vidal, Edurne|||0000-0003-0698-8710 Felip, Eudald|||0000-0002-3812-1313 Puertas, Maria C.|||0000-0002-6750-2318 Oriol-Tordera, Bruna|||0000-0002-2714-9097 Gutiérrez-Chamorro, Lucía|||0000-0002-7649-951X Gohr, André Ruiz Riol, Marta|||0000-0003-1899-8879 Massanella, Marta|||0000-0002-3326-151X Clotet Sala, Bonaventura|||0000-0003-3232-4598 Martínez Picado, Francisco Javier|||0000-0002-4916-2129 Badia, Roger|||0000-0003-3982-7577 Riveira Muñoz, Eva|||0000-0002-6396-1162 Ballana, Ester|||0000-0002-5215-7363 |
| author_role |
author |
| author2 |
García Vidal, Edurne|||0000-0003-0698-8710 Felip, Eudald|||0000-0002-3812-1313 Puertas, Maria C.|||0000-0002-6750-2318 Oriol-Tordera, Bruna|||0000-0002-2714-9097 Gutiérrez-Chamorro, Lucía|||0000-0002-7649-951X Gohr, André Ruiz Riol, Marta|||0000-0003-1899-8879 Massanella, Marta|||0000-0002-3326-151X Clotet Sala, Bonaventura|||0000-0003-3232-4598 Martínez Picado, Francisco Javier|||0000-0002-4916-2129 Badia, Roger|||0000-0003-3982-7577 Riveira Muñoz, Eva|||0000-0002-6396-1162 Ballana, Ester|||0000-0002-5215-7363 |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
HIV-1 cure strategies Innate immunity IRF7 JAK-STAT signalling Latency reversal agents |
| topic |
HIV-1 cure strategies Innate immunity IRF7 JAK-STAT signalling Latency reversal agents |
| description |
The persistence of latent HIV reservoirs allows for viral rebound upon antiretroviral therapy interruption, hindering effective HIV-1 cure. Emerging evidence suggests that modulation of innate immune stimulation could impact viral latency and contribute to the clearing of HIV reservoir. Here, the latency reactivation capacity of a subclass of selective JAK2 inhibitors was characterized as a potential novel therapeutic strategy for HIV-1 cure. Notably, JAK2 inhibitors reversed HIV-1 latency in non-clonal lymphoid and myeloid in vitro models of HIV-1 latency and also ex vivo in CD4+ T cells from ART+ PWH, albeit its function was not dependent on JAK2 expression. Immunophenotypic characterization and whole transcriptomic profiling supported reactivation data, showing common gene expression signatures between latency reactivating agents (LRA; JAK2i fedratinib and PMA) in contrast to other JAK inhibitors, but with significantly fewer affected gene sets in the pathway analysis. In depth evaluation of differentially expressed genes, identified a significant upregulation of IRF7 expression despite the blockade of the JAK-STAT pathway and downregulation of proinflammatory cytokines and chemokines. Moreover, IRF7 expression levels positively correlated with HIV latency reactivation capacity of JAK2 inhibitors and also other common LRAs. Collectively, these results represent a promising step towards HIV eradication by demonstrating the potential of innate immune modulation for reducing the viral reservoir through a novel pathway driven by IRF7. |
| 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/281812 https://dx.doi.org/urn:doi:10.3389/fimmu.2022.1001068 |
| url |
https://ddd.uab.cat/record/281812 https://dx.doi.org/urn:doi:10.3389/fimmu.2022.1001068 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00194 Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-109870RB-I00 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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