HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cells
Introduction: Current antiretroviral therapy (ART) for HIV infection reduces plasma viral loads to undetectable levels and has increased the life expectancy of people with HIV (PWH). However, this increased lifespan is accompanied by signs of accelerated aging and a higher prevalence of age-related...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/223671 |
| Acceso en línea: | https://hdl.handle.net/2445/223671 |
| Access Level: | acceso abierto |
| Palabra clave: | Sida VIH (Virus) Envelliment Metabolisme cel·lular AIDS (Disease) HIV (Viruses) Aging Cell metabolism |
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HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cellsCasanova Güell, VíctorRodríguez-Agustín, AndreaAyala-Suárez, RubénMoraga López, ElisaMaleno, María JoséMallolas Masferrer, JosepMartínez Chamorro, Esteban JoséSánchez-Palomino, SonsolesMiró Meda, José M. (José María), 1956-Alcamí, JoséCliment Vidal, NúriaSidaVIH (Virus)EnvellimentMetabolisme cel·lularAIDS (Disease)HIV (Viruses)AgingCell metabolismIntroduction: Current antiretroviral therapy (ART) for HIV infection reduces plasma viral loads to undetectable levels and has increased the life expectancy of people with HIV (PWH). However, this increased lifespan is accompanied by signs of accelerated aging and a higher prevalence of age-related comorbidities. Tat (Trans-Activator of Transcription) is a key protein for viral replication and pathogenesis. Tat is encoded by 2 exons, with the full-length Tat ranging from 86 to 101 aa (Tat101). Introducing a stop codon in position 73 generates a 1 exon, synthetic 72aa Tat (Tat72). Intracellular, full-length Tat activates the NF-κB pro-inflammatory pathway and increases antiapoptotic signals and ROS generation. These effects may initiate a cellular senescence program, characterized by cell cycle arrest, altered cell metabolism, and increased senescence-associated secretory phenotype (SASP) mediator release However, the precise role of HIV-Tat in inducing a cellular senescence program in CD4+ T-cells is currently unknown. Methods: Jurkat Tetoff cell lines stably transfected with Tat72, Tat101, or an empty vector were used. Flow cytometry and RT-qPCR were used to address senescence biomarkers, and 105 mediators were assessed in cell supernatants with an antibody-based membrane array. Key results obtained in Jurkat-Tat cells were addressed in primary, resting CD4+ T-cells by transient electroporation of HIV-Tat-FLAG plasmid DNA. Results: In the Jurkat cell model, expression of Tat101 increased the levels of the senescence biomarkers BCL-2, CD87, and p21, and increased the release of sCD30, PDGF-AA, and sCD31, among other factors. Tat101 upregulated CD30 and CD31 co-expression in the Jurkat cell surface, distinguishing these cells from Tat72 and Tetoff Jurkats. The percentage of p21+, p16+, and γ-H2AX+ cells were higher in Tat-expressing CD4+ T-cells, detected as a FLAG+ population compared to their FLAG- (Tat negative) counterparts. Increased levels of sCD31 and sCD26 were also detected in electroporated CD4+ T-cell supernatants. Discussion: Intracellular, full-length HIV-Tat expression increases several senescence biomarkers in Jurkat and CD4+ T-cells, and SASP/Aging mediators in cell supernatants. Intracellular HIV-Tat may initiate a cellular senescence program, contributing to the premature aging phenotype observed in PWH.Frontiers Media2025202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfhttps://hdl.handle.net/2445/223671Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2025.1568762Frontiers in Immunology, 2025, num.1568762https://doi.org/10.3389/fimmu.2025.1568762cc-by (c) Casanova, Víctor et al., 2025http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2236712026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cells |
| title |
HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cells |
| spellingShingle |
HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cells Casanova Güell, Víctor Sida VIH (Virus) Envelliment Metabolisme cel·lular AIDS (Disease) HIV (Viruses) Aging Cell metabolism |
| title_short |
HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cells |
| title_full |
HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cells |
| title_fullStr |
HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cells |
| title_full_unstemmed |
HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cells |
| title_sort |
HIV-Tat upregulates the expression of senescence biomarkers in CD4+T-cells |
| dc.creator.none.fl_str_mv |
Casanova Güell, Víctor Rodríguez-Agustín, Andrea Ayala-Suárez, Rubén Moraga López, Elisa Maleno, María José Mallolas Masferrer, Josep Martínez Chamorro, Esteban José Sánchez-Palomino, Sonsoles Miró Meda, José M. (José María), 1956- Alcamí, José Climent Vidal, Núria |
| author |
Casanova Güell, Víctor |
| author_facet |
Casanova Güell, Víctor Rodríguez-Agustín, Andrea Ayala-Suárez, Rubén Moraga López, Elisa Maleno, María José Mallolas Masferrer, Josep Martínez Chamorro, Esteban José Sánchez-Palomino, Sonsoles Miró Meda, José M. (José María), 1956- Alcamí, José Climent Vidal, Núria |
| author_role |
author |
| author2 |
Rodríguez-Agustín, Andrea Ayala-Suárez, Rubén Moraga López, Elisa Maleno, María José Mallolas Masferrer, Josep Martínez Chamorro, Esteban José Sánchez-Palomino, Sonsoles Miró Meda, José M. (José María), 1956- Alcamí, José Climent Vidal, Núria |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Sida VIH (Virus) Envelliment Metabolisme cel·lular AIDS (Disease) HIV (Viruses) Aging Cell metabolism |
| topic |
Sida VIH (Virus) Envelliment Metabolisme cel·lular AIDS (Disease) HIV (Viruses) Aging Cell metabolism |
| description |
Introduction: Current antiretroviral therapy (ART) for HIV infection reduces plasma viral loads to undetectable levels and has increased the life expectancy of people with HIV (PWH). However, this increased lifespan is accompanied by signs of accelerated aging and a higher prevalence of age-related comorbidities. Tat (Trans-Activator of Transcription) is a key protein for viral replication and pathogenesis. Tat is encoded by 2 exons, with the full-length Tat ranging from 86 to 101 aa (Tat101). Introducing a stop codon in position 73 generates a 1 exon, synthetic 72aa Tat (Tat72). Intracellular, full-length Tat activates the NF-κB pro-inflammatory pathway and increases antiapoptotic signals and ROS generation. These effects may initiate a cellular senescence program, characterized by cell cycle arrest, altered cell metabolism, and increased senescence-associated secretory phenotype (SASP) mediator release However, the precise role of HIV-Tat in inducing a cellular senescence program in CD4+ T-cells is currently unknown. Methods: Jurkat Tetoff cell lines stably transfected with Tat72, Tat101, or an empty vector were used. Flow cytometry and RT-qPCR were used to address senescence biomarkers, and 105 mediators were assessed in cell supernatants with an antibody-based membrane array. Key results obtained in Jurkat-Tat cells were addressed in primary, resting CD4+ T-cells by transient electroporation of HIV-Tat-FLAG plasmid DNA. Results: In the Jurkat cell model, expression of Tat101 increased the levels of the senescence biomarkers BCL-2, CD87, and p21, and increased the release of sCD30, PDGF-AA, and sCD31, among other factors. Tat101 upregulated CD30 and CD31 co-expression in the Jurkat cell surface, distinguishing these cells from Tat72 and Tetoff Jurkats. The percentage of p21+, p16+, and γ-H2AX+ cells were higher in Tat-expressing CD4+ T-cells, detected as a FLAG+ population compared to their FLAG- (Tat negative) counterparts. Increased levels of sCD31 and sCD26 were also detected in electroporated CD4+ T-cell supernatants. Discussion: Intracellular, full-length HIV-Tat expression increases several senescence biomarkers in Jurkat and CD4+ T-cells, and SASP/Aging mediators in cell supernatants. Intracellular HIV-Tat may initiate a cellular senescence program, contributing to the premature aging phenotype observed in PWH. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2025 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/223671 |
| url |
https://hdl.handle.net/2445/223671 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2025.1568762 Frontiers in Immunology, 2025, num.1568762 https://doi.org/10.3389/fimmu.2025.1568762 |
| dc.rights.none.fl_str_mv |
cc-by (c) Casanova, Víctor et al., 2025 http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by (c) Casanova, Víctor et al., 2025 http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
16 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Frontiers Media |
| publisher.none.fl_str_mv |
Frontiers Media |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Medicina) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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