ArticleThe Journal of clinical investigation2020
PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Based on the immune system: the role of the IL-2 family in pancreatic disease.Frontiers in immunology · 2025Review
- Adding-on nivolumab to chemotherapy-stabilized patients is associated with improved survival in advanced pancreatic ductal adenocarcinoma.Cancer immunology, immunotherapy : CII · 2024Article
- SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147.Cell communication and signaling : CCS · 2024Review
- Article
- Plasma metabolomics by nuclear magnetic resonance reveals biomarkers and metabolic pathways associated with the control of HIV-1 infection/progression.Frontiers in molecular biosciences · 2023Article
- Null Function of Npr1 Disturbs Immune Response in Colonic Inflammation During Early Postnatal Stage.Inflammation · 2022Article
- Anti-HIV Activity of Snake Venom Phospholipase A2s: Updates for New Enzymes and Different Virus Strains.International journal of molecular sciences · 2022Article
- Microbial Protein Binding to gC1qR Drives PLA2G1B-Induced CD4 T-Cell Anergy.Frontiers in immunology · 2022Article
- Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase AFrontiers in cell and developmental biology · 2022Article
- More than a Gender Issue: Testis as a Distinctive HIV Reservoir and Its Implication for Viral Eradication.Methods in molecular biology (Clifton, N.J.) · 2022Article
- What do secreted phospholipases ABiochimie · 2021Review
- Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART.PLoS pathogens · 2021Article
- MicroPhenoDB Associates Metagenomic Data with Pathogenic Microbes, Microbial Core Genes, and Human Disease Phenotypes.Genomics, proteomics & bioinformatics · 2020Article
- Updating Phospholipase ABiomolecules · 2020Review
- Sharing CD4+ T Cell Loss: When COVID-19 and HIV Collide on Immune System.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The precise mechanism leading to profound immunodeficiency of HIV-infected patients is still only partially understood. Here, we show that more than 80% of CD4+ T cells from HIV-infected patients have morphological abnormalities. Their membranes exhibited numerous large abnormal membrane microdomains (aMMDs), which trap and inactivate physiological receptors, such as that for IL-7. In patient plasma, we identified phospholipase A2 group IB (PLA2G1B) as the key molecule responsible for the formation of aMMDs. At physiological concentrations, PLA2G1B synergized with the HIV gp41 envelope protein, which appears to be a driver that targets PLA2G1B to the CD4+ T cell surface. The PLA2G1B/gp41 pair induced CD4+ T cell unresponsiveness (anergy). At high concentrations in vitro, PLA2G1B acted alone, independently of gp41, and inhibited the IL-2, IL-4, and IL-7 responses, as well as TCR-mediated activation and proliferation, of CD4+ T cells. PLA2G1B also decreased CD4+ T cell survival in vitro, likely playing a role in CD4 lymphopenia in conjunction with its induced IL-7 receptor defects. The effects on CD4+ T cell anergy could be blocked by a PLA2G1B-specific neutralizing mAb in vitro and in vivo. The PLA2G1B/gp41 pair constitutes what we believe is a new mechanism of immune dysfunction and a compelling target for boosting immune responses in HIV-infected patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.