HIV-1 Nef protein down-regulates several cell surface receptors through its interference with the cell sorting and trafficking machinery. Here we demonstrate for the first time the ability of Nef to down-regulate cell surface expression of the negative immune modulator CTLA-4. Down-regulation of CTLA-4 required the Nef motifs DD175, EE155 and LL165, all known to be involved in vesicle trafficking. Disruption of the lysosomal functions by pH-neutralizing agents prevented CTLA-4 down-regulation by Nef, demonstrating the implication of the endosomal/lysosomal compartments in this process. Confocal microscopy experiments visualized the co-localization between Nef and CTLA-4 in the early and recycling endosomes but not at the cell surface. Overall, our results provide a novel mechanism by which HIV-1 Nef interferes with the surface expression of the negative regulator of T cell activation CTLA-4. Down-regulation of CTLA-4 may contribute to the mechanisms by which HIV-1 sustains T cell activation, a critical step in viral replication and dissemination.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553160 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0054295 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3.
Oncol Res
December 2024
China-America Cancer Research Institute, Guangdong Medical University, Dongguan, 523808, China.
Background: Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.
Methods: We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases.
Reduced Deltex1 expression in T cells indicates increased disease activity in Sjögren's disease.
Clin Exp Rheumatol
December 2024
Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, and Division of Allergy, Immunology & Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Objectives: Deltex1 is a transcriptional target of NFAT that promotes T cell anergy. However, whether Deltex1 affects the properties of regulatory T cells (Tregs), which are involved in the pathogenesis of Sjögren's disease (SjD), is unknown.
Methods: T cells were purified from peripheral blood using a negative selection method.
CD55 characterizes regulatory T cells with reduced functionality and is downregulated in rheumatoid arthritis.
Int Immunopharmacol
January 2025
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China. Electronic address:
Objective: This study aimed to investigate the role of CD55 in regulatory T cells (Tregs) and clarify its clinical relevance in rheumatoid arthritis (RA).
Methods: Flow cytometry was used to examine the expression of Helios and CTLA-4 in CD55 + and CD55- Tregs in mouse peripheral blood and spleen. FoxP3 mice were employed to analyze the in vitro inhibitory function of CD55 + and CD55-Tregs.
Echinacoside inhibits tumor immune evasion by downregulating inducible PD-L1 and reshaping tumor immune landscape in breast and colorectal cancer.
Phytomedicine
December 2024
Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:
Background: Targeting PD-L1 has become a crucial approach in tumor immunotherapy. Echinacoside (ECH) is a natural compound known for its extensive biological activities, its impact on antitumor immunity remains uncertain.
Purpose: This work was designed to assess the effects of ECH on the PD-L1/PD-1-mediated tumor immune evasion and its underlying mechanisms.
YTHDF3 phase separation regulates HSPA13-dependent clear cell renal cell carcinoma development and immune evasion.
Cancer Sci
August 2024
Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Insufficient understanding about the immune evasion mechanism leads to the inability in predicting current immunotherapy effects in clear cell renal cell carcinoma (ccRCC) and sensitizing ccRCC to immunotherapy. RNA binding proteins (RBPs) can promote tumor progression and immune evasion. However, research on RBPs, particularly m6A reader YTHDF3, in ccRCC development and immune evasion is limited.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!