RT info:eu-repo/semantics/article
T1 TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness.
A1 Valenzuela Fernández, Agustín
A1 Cabrera Rodríguez, Romina
A1 Pérez Yanes, Silvia
A1 Lorenzo Sánchez, Iria
A1 Estévez Herrera, Judith
A1 García Luis, Jonay
A1 Trujillo González, Rodrigo Francisco
K1 TARDBP/TDP-43
K1 HDAC6
K1 autophagy
K1 viral production
K1 HIV-1 infection capacity
AB The transactive response DNA-binding protein (TARDBP/TDP-43) is known to stabilizethe anti-HIV-1 factor, histone deacetylase 6 (HDAC6). TDP-43 has been reported to determine cellpermissivity to HIV-1 fusion and infection acting on tubulin-deacetylase HDAC6. Here, we studiedthe functional involvement of TDP-43 in the late stages of the HIV-1 viral cycle. The overexpressionof TDP-43, in virus-producing cells, stabilized HDAC6 (i.e., mRNA and protein) and triggeredthe autophagic clearance of HIV-1 Pr55Gag and Vif proteins. These events inhibited viral particleproduction and impaired virion infectiveness, observing a reduction in the amount of Pr55Gag and Vifproteins incorporated into virions. A nuclear localization signal (NLS)-TDP-43 mutant was not able tocontrol HIV-1 viral production and infection. Likewise, specific TDP-43-knockdown reduced HDAC6expression (i.e., mRNA and protein) and increased the expression level of HIV-1 Vif and Pr55Gagproteins and α-tubulin acetylation. Thus, TDP-43 silencing favored virion production and enhancedvirus infectious capacity, thereby increasing the amount of Vif and Pr55Gag proteins incorporated intovirions. Noteworthy, there was a direct relationship between the content of Vif and Pr55Gag proteinsin virions and their infection capacity. Therefore, for TDP-43, the TDP-43/HDAC6 axis could beconsidered a key factor to control HIV-1 viral production and virus infectiveness.
SN 1422-0067
YR 2023
FD 2023
LK http://riull.ull.es/xmlui/handle/915/35340
UL http://riull.ull.es/xmlui/handle/915/35340
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 27-jun-2024