RT info:eu-repo/semantics/article
T1 Transactive Response DNA- Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV- 1 Infection by Acting on HDAC6.
A1 Valenzuela Fernández, Agustín
A1 Cabrera Rodríguez, Romina
A1 Pérez Yanes, Silvia
A1 Montelongo, Rafaela
A1 Lorenzo Salazar, José M.
A1 Estévez Herrera, Judith
A1 García Luis, Jonay
A1 Íñigo Campos, Antonio
A1 Rubio Rodríguez, Luis A.
A1 Muñoz Barrera, Adrián
A1 Trujillo González, Rodrigo Francisco
A1 Dorta Guerra, Roberto
A1 Casado, Concha
A1 Pernas, María
A1 Blanco, Julià
A1 Flores, Carlos
A2 Medicina Física y Farmacología
A2 Grupo "Inmunología Celular y Viral"
K1 TARDBP/TDP-43
K1 HDAC6
K1 pore fusion formation
K1 cell-permissivity
K1 HIV-1 infection
AB 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-43activity 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 impairedHIV-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 levelsnegatively affected viral Env fusion capacity. Silencing of endogenous TDP-43 significantly decreasedHDAC6 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 stronglyreduced 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-progressorelite controllers (LTNP-EC). On the contrary, silencing endogenous TDP-43 significantly favored theinfectivity of primary Envs from VNP and RP individuals, and notably increased the infection ofthose from LTNP-EC. Taken together, our results indicate that TDP-43 shapes cell permissivity toHIV-1 infection, affecting viral Env fusion and infection capacities by altering the HDAC6 levels andassociated tubulin-deacetylase anti-HIV-1 activity
YR 2022
FD 2022
LK http://riull.ull.es/xmlui/handle/915/35372
UL http://riull.ull.es/xmlui/handle/915/35372
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 29-may-2024