Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/15178
Título
Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6
Autor(es)
Cabrera-Rodríguez, Romina | Pérez-Yanes, Silvia | Montelongo, Rafaela | Lorenzo-Salazar, José M | Estévez-Herrera, Judith | García-Luis, Jonay | Íñigo-Campos, Antonio | Rubio-Rodríguez, Luis A | Muñoz-Barrera, Adrián | Trujillo-González, Rodrigo | Dorta-Guerra, Roberto | Casado, Concepcion ISCIII | Pernas, Maria ISCIII | Blanco, Julià | Flores, Carlos | Valenzuela-Fernández, Agustín
Fecha de publicación
2022-05-31
Cita
Int J Mol Sci. 2022 May 31;23(11):6180.
Idioma
Inglés
Tipo de documento
research article
Resumen
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.
Palabras clave
MESH
Versión en línea
DOI
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