Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL
HIV infection mediates the apoptosis of lymphocytes, the mechanism of which is multifaceted. Here, we evaluated the role of Wnt/β-catenin signaling in HIV-associated T cell apoptosis, as Wnt/β-catenin regulates the transcriptional activity of genes impacting apoptosis. We specifically investigated t...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/14/7/1469 |
| _version_ | 1797415070324490240 |
|---|---|
| author | Yasmeen A. Albalawi Srinivas D. Narasipura Lena Al-Harthi |
| author_facet | Yasmeen A. Albalawi Srinivas D. Narasipura Lena Al-Harthi |
| author_sort | Yasmeen A. Albalawi |
| collection | DOAJ |
| description | HIV infection mediates the apoptosis of lymphocytes, the mechanism of which is multifaceted. Here, we evaluated the role of Wnt/β-catenin signaling in HIV-associated T cell apoptosis, as Wnt/β-catenin regulates the transcriptional activity of genes impacting apoptosis. We specifically investigated the role of the Wnt/β-catenin pathway in the HIV-associated apoptosis of CD4+ T cells and CD4<sup>dim</sup>CD8<sup>bright</sup> T cells, a population that is infected by HIV. We found that the induction of β-catenin, via a 6-bromoindirubin-3-oxime (BIO), significantly rescued HIV-infected CD4+ and CD4<sup>dim</sup>CD8<sup>bright</sup> T cells from apoptosis by >40–50%. Further, a small-molecule inhibitor of the Wnt/β-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/β-catenin, in CD4+ and CD4<sup>dim</sup>CD8<sup>bright</sup> T cells by approximately 3-fold. Inhibiting Bcl-xL by WEHI-539 abrogated β-catenin-mediated apoptotic protection in infected CD4+ and CD4<sup>dim</sup>CD8<sup>bright</sup> T cells. Collectively, these findings demonstrate that engaging Wnt/β-catenin signaling in HIV-infected T cells protects them from HIV-associated apoptosis by inducing Bcl-xL. |
| first_indexed | 2024-03-09T05:42:44Z |
| format | Article |
| id | doaj.art-fe53f54800184e4d91726ba56ffeb3a4 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T05:42:44Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-fe53f54800184e4d91726ba56ffeb3a42023-12-03T12:24:05ZengMDPI AGViruses1999-49152022-07-01147146910.3390/v14071469Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xLYasmeen A. Albalawi0Srinivas D. Narasipura1Lena Al-Harthi2Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USADepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USAHIV infection mediates the apoptosis of lymphocytes, the mechanism of which is multifaceted. Here, we evaluated the role of Wnt/β-catenin signaling in HIV-associated T cell apoptosis, as Wnt/β-catenin regulates the transcriptional activity of genes impacting apoptosis. We specifically investigated the role of the Wnt/β-catenin pathway in the HIV-associated apoptosis of CD4+ T cells and CD4<sup>dim</sup>CD8<sup>bright</sup> T cells, a population that is infected by HIV. We found that the induction of β-catenin, via a 6-bromoindirubin-3-oxime (BIO), significantly rescued HIV-infected CD4+ and CD4<sup>dim</sup>CD8<sup>bright</sup> T cells from apoptosis by >40–50%. Further, a small-molecule inhibitor of the Wnt/β-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/β-catenin, in CD4+ and CD4<sup>dim</sup>CD8<sup>bright</sup> T cells by approximately 3-fold. Inhibiting Bcl-xL by WEHI-539 abrogated β-catenin-mediated apoptotic protection in infected CD4+ and CD4<sup>dim</sup>CD8<sup>bright</sup> T cells. Collectively, these findings demonstrate that engaging Wnt/β-catenin signaling in HIV-infected T cells protects them from HIV-associated apoptosis by inducing Bcl-xL.https://www.mdpi.com/1999-4915/14/7/1469HIVapoptosisWnt/β-catenin pathwayCD4 T cellsCD4<sup>dim</sup>CD8<sup>bright</sup> T cellsBcl-xL |
| spellingShingle | Yasmeen A. Albalawi Srinivas D. Narasipura Lena Al-Harthi Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL Viruses HIV apoptosis Wnt/β-catenin pathway CD4 T cells CD4<sup>dim</sup>CD8<sup>bright</sup> T cells Bcl-xL |
| title | Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL |
| title_full | Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL |
| title_fullStr | Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL |
| title_full_unstemmed | Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL |
| title_short | Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL |
| title_sort | wnt β catenin protects lymphocytes from hiv mediated apoptosis via induction of bcl xl |
| topic | HIV apoptosis Wnt/β-catenin pathway CD4 T cells CD4<sup>dim</sup>CD8<sup>bright</sup> T cells Bcl-xL |
| url | https://www.mdpi.com/1999-4915/14/7/1469 |
| work_keys_str_mv | AT yasmeenaalbalawi wntbcateninprotectslymphocytesfromhivmediatedapoptosisviainductionofbclxl AT srinivasdnarasipura wntbcateninprotectslymphocytesfromhivmediatedapoptosisviainductionofbclxl AT lenaalharthi wntbcateninprotectslymphocytesfromhivmediatedapoptosisviainductionofbclxl |