2026-04-29T04:09:11Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/151782024-09-27T23:10:43Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Cabrera-Rodríguez, Romina author Pérez-Yanes, Silvia author Montelongo, Rafaela author Lorenzo-Salazar, José M author Estévez-Herrera, Judith author García-Luis, Jonay author Íñigo-Campos, Antonio author Rubio-Rodríguez, Luis A author Muñoz-Barrera, Adrián author Trujillo-González, Rodrigo author Dorta-Guerra, Roberto author Casado, Concepcion author Pernas, Maria author Blanco, Julià author Flores, Carlos author Valenzuela-Fernández, Agustín author 2022-05-31 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. Int J Mol Sci. 2022 May 31;23(11):6180. http://hdl.handle.net/20.500.12105/15178 35682862 10.3390/ijms23116180 1422-0067 International journal of molecular sciences TARDBP/TDP-43 HDAC6 Pore fusion formation Cell-permissivity HIV-1 infection Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6