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Transactive Response DNA- Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV- 1 Infection by Acting on HDAC6.
dc.contributor.author | Valenzuela Fernández, Agustín | |
dc.contributor.author | Cabrera Rodríguez, Romina | |
dc.contributor.author | Pérez Yanes, Silvia | |
dc.contributor.author | Montelongo, Rafaela | |
dc.contributor.author | Lorenzo Salazar, José M. | |
dc.contributor.author | Estévez Herrera, Judith | |
dc.contributor.author | García Luis, Jonay | |
dc.contributor.author | Íñigo Campos, Antonio | |
dc.contributor.author | Rubio Rodríguez, Luis A. | |
dc.contributor.author | Muñoz Barrera, Adrián | |
dc.contributor.author | Trujillo González, Rodrigo Francisco | |
dc.contributor.author | Dorta Guerra, Roberto | |
dc.contributor.author | Casado, Concha | |
dc.contributor.author | Pernas, María | |
dc.contributor.author | Blanco, Julià | |
dc.contributor.author | Flores, Carlos | |
dc.contributor.other | Medicina Física y Farmacología | |
dc.contributor.other | Grupo "Inmunología Celular y Viral" | |
dc.date.accessioned | 2024-01-15T21:10:24Z | |
dc.date.available | 2024-01-15T21:10:24Z | |
dc.date.issued | 2022 | |
dc.identifier.uri | http://riull.ull.es/xmlui/handle/915/35372 | |
dc.description.abstract | 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 | en |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | |
dc.relation.ispartofseries | International Journal of Molecular Science, 2022, 23, 6180. | |
dc.rights | Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional) | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES | |
dc.title | Transactive Response DNA- Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV- 1 Infection by Acting on HDAC6. | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.3390/ijms23116180 | |
dc.subject.keyword | TARDBP/TDP-43 | en |
dc.subject.keyword | HDAC6 | en |
dc.subject.keyword | pore fusion formation | en |
dc.subject.keyword | cell-permissivity | en |
dc.subject.keyword | HIV-1 infection | en |