Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6.

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 Env

SUBMITTER: Cabrera-Rodriguez R 

PROVIDER: S-EPMC9181786 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature