Bibliographic Details
| Title: |
PD-1 suppression enhances HIV reactivation and T-cell immunity via MAPK/NF-κB signaling |
| Authors: |
Xueru Lin, Bo Song, Lijun Cao, Lin Zhang, Siyu Liu, Xue Wang, Xiaohong Chen, Shuchen Li |
| Source: |
European Journal of Medical Research, Vol 30, Iss 1, Pp 1-10 (2025) |
| Publisher Information: |
BMC, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
PD-1, HIV infection, T-cell function, MAPK/NF-κB signaling pathway, Immune escape, Medicine |
| More Details: |
Abstract Background Programmed cell death protein 1 (PD-1) is a key immune checkpoint involved in HIV-related immune escape, but its precise role and underlying mechanisms remain unclear. This study investigates the effects of PD-1 inhibition on HIV infection and T-cell function, focusing on the MAPK and NF-κB signaling pathways. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from HIV-infected individuals and healthy controls. T-cell subsets were analyzed for PD-1 expression via flow cytometry. The impact of antiretroviral therapy (ART) on T-cell numbers, apoptosis, and PD-1 expression was assessed. PD-1 blockade was performed using pembrolizumab, and its effects on T-cell survival and cytokine secretion were evaluated. MAPK/NF-κB signaling was analyzed using Western blot and co-immunoprecipitation, while latent HIV activation was assessed by measuring HIV-1 LTR transcriptional activity in J-Lat cells. Reverse-ChIP assays explored the interaction between HIV-1 Nef protein and the PD-1 promoter. Results PD-1 expression was higher in T cells from HIV-infected individuals compared to healthy controls, with no significant change following ART. PD-1 blockade with pembrolizumab reduced T-cell apoptosis and enhanced cytokine secretion (TNF-α, IFN-γ, IL-2). PD-1 inhibition also activated latent HIV in J-Lat cells. Western blotting revealed reduced phosphorylation of MAPK and NF-κB pathway components (p-MEK1/2, p-p38 MAPK, p-NF-κB p65), and co-immunoprecipitation confirmed a direct interaction between PD-1 and SHP-2, regulating these pathways. Conclusions PD-1 mediates HIV immune evasion through the MAPK/NF-κB pathways. PD-1 blockade restores T-cell function and activates latent HIV, suggesting potential therapeutic strategies for HIV treatment. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2047-783X |
| Relation: |
https://doaj.org/toc/2047-783X |
| DOI: |
10.1186/s40001-025-02427-4 |
| Access URL: |
https://doaj.org/article/452226ac46dc4937abcc3fd4cb0621b6 |
| Accession Number: |
edsdoj.452226ac46dc4937abcc3fd4cb0621b6 |
| Database: |
Directory of Open Access Journals |
