TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness

Cabrera-Rodríguez, Romina; Pérez-Yanes, Silvia; Lorenzo-Sánchez, Iria; Estévez-Herrera, Judith; García-Luis, Jonay; Trujillo-González, Rodrigo; Valenzuela-Fernández, Agustín

doi:10.3390/ijms24087658

Open AccessArticle

TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness

by

Romina Cabrera-Rodríguez

^1,*

,

Silvia Pérez-Yanes

¹,

Iria Lorenzo-Sánchez

¹,

Judith Estévez-Herrera

¹,

Jonay García-Luis

¹

,

Rodrigo Trujillo-González

^1,2

and

Agustín Valenzuela-Fernández

^1,*

¹

Laboratorio “Inmunología Celular y Viral”, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna (ULL), 38320 La Laguna, Tenerife, Spain

²

Analysis Department, Faculty of Mathematics, Universidad de La Laguna (ULL), 38296 La Laguna, Tenerife, Spain

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2023, 24(8), 7658; https://doi.org/10.3390/ijms24087658

Submission received: 4 April 2023 / Revised: 16 April 2023 / Accepted: 18 April 2023 / Published: 21 April 2023

(This article belongs to the Special Issue Molecular Advances in Infectious Disease)

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Abstract

The transactive response DNA-binding protein (TARDBP/TDP-43) is known to stabilize the anti-HIV-1 factor, histone deacetylase 6 (HDAC6). TDP-43 has been reported to determine cell permissivity to HIV-1 fusion and infection acting on tubulin-deacetylase HDAC6. Here, we studied the functional involvement of TDP-43 in the late stages of the HIV-1 viral cycle. The overexpression of TDP-43, in virus-producing cells, stabilized HDAC6 (i.e., mRNA and protein) and triggered the autophagic clearance of HIV-1 Pr55^Gag and Vif proteins. These events inhibited viral particle production and impaired virion infectiveness, observing a reduction in the amount of Pr55^Gag and Vif proteins incorporated into virions. A nuclear localization signal (NLS)-TDP-43 mutant was not able to control HIV-1 viral production and infection. Likewise, specific TDP-43-knockdown reduced HDAC6 expression (i.e., mRNA and protein) and increased the expression level of HIV-1 Vif and Pr55^Gag proteins and α-tubulin acetylation. Thus, TDP-43 silencing favored virion production and enhanced virus infectious capacity, thereby increasing the amount of Vif and Pr55^Gag proteins incorporated into virions. Noteworthy, there was a direct relationship between the content of Vif and Pr55^Gag proteins in virions and their infection capacity. Therefore, for TDP-43, the TDP-43/HDAC6 axis could be considered a key factor to control HIV-1 viral production and virus infectiveness.

Keywords: TARDBP/TDP-43; HDAC6; autophagy; viral production; HIV-1 infection capacity

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MDPI and ACS Style

Cabrera-Rodríguez, R.; Pérez-Yanes, S.; Lorenzo-Sánchez, I.; Estévez-Herrera, J.; García-Luis, J.; Trujillo-González, R.; Valenzuela-Fernández, A. TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness. Int. J. Mol. Sci. 2023, 24, 7658. https://doi.org/10.3390/ijms24087658

AMA Style

Cabrera-Rodríguez R, Pérez-Yanes S, Lorenzo-Sánchez I, Estévez-Herrera J, García-Luis J, Trujillo-González R, Valenzuela-Fernández A. TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness. International Journal of Molecular Sciences. 2023; 24(8):7658. https://doi.org/10.3390/ijms24087658

Chicago/Turabian Style

Cabrera-Rodríguez, Romina, Silvia Pérez-Yanes, Iria Lorenzo-Sánchez, Judith Estévez-Herrera, Jonay García-Luis, Rodrigo Trujillo-González, and Agustín Valenzuela-Fernández. 2023. "TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness" International Journal of Molecular Sciences 24, no. 8: 7658. https://doi.org/10.3390/ijms24087658

APA Style

Cabrera-Rodríguez, R., Pérez-Yanes, S., Lorenzo-Sánchez, I., Estévez-Herrera, J., García-Luis, J., Trujillo-González, R., & Valenzuela-Fernández, A. (2023). TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness. International Journal of Molecular Sciences, 24(8), 7658. https://doi.org/10.3390/ijms24087658

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TDP-43 Controls HIV-1 Viral Production and Virus Infectiveness

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