Wnt/ß-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL.
Viruses
; 14(7)2022 07 02.
Article
en En
| MEDLINE
| ID: mdl-35891449
ABSTRACT
HIV infection mediates the apoptosis of lymphocytes, the mechanism of which is multifaceted. Here, we evaluated the role of Wnt/ß-catenin signaling in HIV-associated T cell apoptosis, as Wnt/ß-catenin regulates the transcriptional activity of genes impacting apoptosis. We specifically investigated the role of the Wnt/ß-catenin pathway in the HIV-associated apoptosis of CD4+ T cells and CD4dimCD8bright T cells, a population that is infected by HIV. We found that the induction of ß-catenin, via a 6-bromoindirubin-3-oxime (BIO), significantly rescued HIV-infected CD4+ and CD4dimCD8bright T cells from apoptosis by >40−50%. Further, a small-molecule inhibitor of the Wnt/ß-catenin pathway (PNU-74654) reversed BIO-mediated protection from HIV-associated apoptosis. BIO also induced Bcl-xL, an anti-apoptotic protein, and a target gene of Wnt/ß-catenin, in CD4+ and CD4dimCD8bright T cells by approximately 3-fold. Inhibiting Bcl-xL by WEHI-539 abrogated ß-catenin-mediated apoptotic protection in infected CD4+ and CD4dimCD8bright T cells. Collectively, these findings demonstrate that engaging Wnt/ß-catenin signaling in HIV-infected T cells protects them from HIV-associated apoptosis by inducing Bcl-xL.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
Beta Catenina
Límite:
Humans
Idioma:
En
Revista:
Viruses
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos