NDLI: PD-1 suppression enhances HIV reactivation and T-cell immunity via MAPK/NF-κB signaling

Content Provider	Springer Nature : BioMed Central
Author	Lin, Xueru Song, Bo Cao, Lijun Zhang, Lin Liu, Siyu Wang, Xue Chen, Xiaohong Li, Shuchen
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.
Related Links	https://eurjmedres.biomedcentral.com/counter/pdf/10.1186/s40001-025-02427-4.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s40001-025-02427-4
Journal	European Journal of Medical Research
Issue Number	1
Volume Number	30
Language	English
Publisher	BioMed Central
Publisher Date	2025-04-04
Access Restriction	Open
Subject Keyword	Medicine Public Health Infectious Diseases Internal Medicine Surgery Oncology Biomedicine PD-1 HIV infection T-cell function MAPK/NF-κB signaling pathway Immune escape Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Medicine
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	2.9/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

A2AR regulate inflammation through PKA/NF-κB signaling pathways in intervertebral disc degeneration

Astragalus polysaccharide enhances the immune function of RAW264.7 macrophages via the NF-κB p65/MAPK signaling pathway.

Down-regulation of S100A9 inhibits osteosarcoma cell growth through inactivating MAPK and NF-κB signaling pathways

Changes in the BTK/NF-κB signaling pathway and related cytokines in different stages of neuromyelitis optica spectrum disorders

S100A4 suppresses cancer stem cell proliferation via interaction with the IKK/NF-κB signaling pathway

High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells

NF-κB pathway and angiogenesis: insights into colorectal cancer development and therapeutic targets

miRNAs regulate immune response and signaling during hepatitis C virus infection

CD8⁺ Cytotoxic T Lymphocyte Responses and Viral Epitope Escape in Acute HIV-1 Infection.

PD-1 suppression enhances HIV reactivation and T-cell immunity via MAPK/NF-κB signaling

Similar Documents

A2AR regulate inflammation through PKA/NF-κB signaling pathways in intervertebral disc degeneration

Astragalus polysaccharide enhances the immune function of RAW264.7 macrophages via the NF-κB p65/MAPK signaling pathway.

Down-regulation of S100A9 inhibits osteosarcoma cell growth through inactivating MAPK and NF-κB signaling pathways

Changes in the BTK/NF-κB signaling pathway and related cytokines in different stages of neuromyelitis optica spectrum disorders

S100A4 suppresses cancer stem cell proliferation via interaction with the IKK/NF-κB signaling pathway

High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells

NF-κB pathway and angiogenesis: insights into colorectal cancer development and therapeutic targets

miRNAs regulate immune response and signaling during hepatitis C virus infection

CD8+ Cytotoxic T Lymphocyte Responses and Viral Epitope Escape in Acute HIV-1 Infection.

PD-1 suppression enhances HIV reactivation and T-cell immunity via MAPK/NF-κB signaling

CD8⁺ Cytotoxic T Lymphocyte Responses and Viral Epitope Escape in Acute HIV-1 Infection.