Browsing by Keyword "HIV-1 infection"
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Publication Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6(Multidisciplinary Digital Publishing Institute (MDPI), 2022-05-31) 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; Pernas, Maria; Blanco, Julià; Flores, Carlos; Valenzuela-Fernández, Agustín; Red de Investigación Cooperativa en Investigación en Sida (España); Plan Nacional de I+D+i (España); Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Government of Catalonia (España); Ministerio de Asuntos Económicos y Transformación Digital (España); Gobierno de Canarias (España); Instituto Tecnológico y de Energías Renovables (España); Ministerio de Ciencia e Innovación (España); Ministerio de Ciencia, Innovación y Universidades (España); Agencia Canaria de Investigación, Innovación y Sociedad de la Información; Unión Europea. Fondo Social Europeo (ESF/FSE); Fundación CajaCanarias; Fundación Doctor Manuel Morales; Agencia Estatal de Investigación (España)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.