Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6
The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism. Consistently, using an HIV-1 Env-mediated cell-to-cell fusion model, the overexpression of TDP-43 levels negatively affected viral Env fusion capacity. Silencing of endogenous TDP-43 significantly decreased HDAC6 levels and increased the fusogenic and infection activities of the HIV-1 Env. Using pseudovirus bearing primary viral Envs from HIV-1 individuals, overexpression of wt-TDP-43 strongly reduced the infection activity of Envs from viremic non-progressors (VNP) and rapid progressors (RP) patients down to the levels of the inefficient HIV-1 Envs observed in long-term non-progressor elite controllers (LTNP-EC). On the contrary, silencing endogenous TDP-43 significantly favored the infectivity of primary Envs from VNP and RP individuals, and notably increased the infection of those from LTNP-EC. Taken together, our results indicate that TDP-43 shapes cell permissivity to HIV-1 infection, affecting viral Env fusion and infection capacities by altering the HDAC6 levels and associated tubulin-deacetylase anti-HIV-1 activity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
International journal of molecular sciences - 23(2022), 11 vom: 31. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cabrera-Rodríguez, Romina [VerfasserIn] |
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| Links: |
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| Themen: |
Cell-permissivity |
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| Anmerkungen: |
Date Completed 13.06.2022 Date Revised 16.07.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms23116180 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM342045601 |
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| 245 | 1 | 0 | |a Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6 |
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| 500 | |a Date Revised 16.07.2022 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism. Consistently, using an HIV-1 Env-mediated cell-to-cell fusion model, the overexpression of TDP-43 levels negatively affected viral Env fusion capacity. Silencing of endogenous TDP-43 significantly decreased HDAC6 levels and increased the fusogenic and infection activities of the HIV-1 Env. Using pseudovirus bearing primary viral Envs from HIV-1 individuals, overexpression of wt-TDP-43 strongly reduced the infection activity of Envs from viremic non-progressors (VNP) and rapid progressors (RP) patients down to the levels of the inefficient HIV-1 Envs observed in long-term non-progressor elite controllers (LTNP-EC). On the contrary, silencing endogenous TDP-43 significantly favored the infectivity of primary Envs from VNP and RP individuals, and notably increased the infection of those from LTNP-EC. Taken together, our results indicate that TDP-43 shapes cell permissivity to HIV-1 infection, affecting viral Env fusion and infection capacities by altering the HDAC6 levels and associated tubulin-deacetylase anti-HIV-1 activity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HDAC6 | |
| 650 | 4 | |a HIV-1 infection | |
| 650 | 4 | |a TARDBP/TDP-43 | |
| 650 | 4 | |a cell-permissivity | |
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| 700 | 1 | |a Pérez-Yanes, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Montelongo, Rafaela |e verfasserin |4 aut | |
| 700 | 1 | |a Lorenzo-Salazar, José M |e verfasserin |4 aut | |
| 700 | 1 | |a Estévez-Herrera, Judith |e verfasserin |4 aut | |
| 700 | 1 | |a García-Luis, Jonay |e verfasserin |4 aut | |
| 700 | 1 | |a Íñigo-Campos, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Rubio-Rodríguez, Luis A |e verfasserin |4 aut | |
| 700 | 1 | |a Muñoz-Barrera, Adrián |e verfasserin |4 aut | |
| 700 | 1 | |a Trujillo-González, Rodrigo |e verfasserin |4 aut | |
| 700 | 1 | |a Dorta-Guerra, Roberto |e verfasserin |4 aut | |
| 700 | 1 | |a Casado, Concha |e verfasserin |4 aut | |
| 700 | 1 | |a Pernas, María |e verfasserin |4 aut | |
| 700 | 1 | |a Blanco, Julià |e verfasserin |4 aut | |
| 700 | 1 | |a Flores, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Valenzuela-Fernández, Agustín |e verfasserin |4 aut | |
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