ArticlePLoS pathogens2010
HIV gp41 engages gC1qR on CD4+ T cells to induce the expression of an NK ligand through the PIP3/H2O2 pathway.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 85 citations in OpenAlex.
- HBV p22-interacting protein C1QBP inhibits viral replication through impeding nucleocapsid formation and nuclear import.PLoS pathogens · 2025Article
- The Potential of PIP3 in Enhancing Wound Healing.International journal of molecular sciences · 2024Article
- Targeting tumor cell-to-macrophage communication by blocking Vtn-C1qbp interaction inhibits tumor progression via enhancing macrophage phagocytosis.Theranostics · 2024Article
- The chaperone protein p32 stabilizes HIV-1 Tat and strengthens the p-TEFb/RNAPII/TAR complex promoting HIV transcription elongation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of gC1qR as a modulator of endothelial cell permeability and contributor to post-stroke inflammation and edema formation.Frontiers in cellular neuroscience · 2023Review
- An approach to p32/gC1qR/HABP1: a multifunctional protein with an essential role in cancer.Journal of cancer research and clinical oncology · 2022Review
- Human C1q Regulates Influenza A Virus Infection and Inflammatory Response via Its Globular Domain.International journal of molecular sciences · 2022Article
- HIV Infection Predisposes to Increased Chances of HBV Infection: Current Understanding of the Mechanisms Favoring HBV Infection at Each Clinical Stage of HIV Infection.Frontiers in immunology · 2022Review
- Microbial Protein Binding to gC1qR Drives PLA2G1B-Induced CD4 T-Cell Anergy.Frontiers in immunology · 2022Article
- Review
- Innate Immune Response Against HIV-1.Advances in experimental medicine and biology · 2021Article
- HCV Core Protein Induces Chemokine CCL2 and CXCL10 Expression Through NF-κB Signaling Pathway in Macrophages.Frontiers in immunology · 2021Article
- PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients.The Journal of clinical investigation · 2020Article
- In the Crosshairs: RNA Viruses OR Complement?Frontiers in immunology · 2020Review
- SLE: Novel Postulates for Therapeutic Options.Frontiers in immunology · 2020Review
- Vaccines against Ebola virus and Marburg virus: recent advances and promising candidates.Human vaccines & immunotherapeutics · 2019Review
- Effect of anti-retroviral therapy on oxidative stress in hospitalized HIV-infected adults with and without TB.African health sciences · 2018Article
- Review
- C-Type Lectin Receptors in Antiviral Immunity and Viral Escape.Frontiers in immunology · 2018Review
- Antigenic and immunosuppressive properties of a trimeric recombinant transmembrane envelope protein gp41 of HIV-1.PloS one · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4(+) T cell loss is central to HIV pathogenesis. In the initial weeks post-infection, the great majority of dying cells are uninfected CD4(+) T cells. We previously showed that the 3S motif of HIV-1 gp41 induces surface expression of NKp44L, a cellular ligand for an activating NK receptor, on uninfected bystander CD4(+) T cells, rendering them susceptible to autologous NK killing. However, the mechanism of the 3S mediated NKp44L surface expression on CD4(+) T cells remains unknown. Here, using immunoprecipitation, ELISA and blocking antibodies, we demonstrate that the 3S motif of HIV-1 gp41 binds to gC1qR on CD4(+) T cells. We also show that the 3S peptide and two endogenous gC1qR ligands, C1q and HK, each trigger the translocation of pre-existing NKp44L molecules through a signaling cascade that involves sequential activation of PI3K, NADPH oxidase and p190 RhoGAP, and TC10 inactivation. The involvement of PI3K and NADPH oxidase derives from 2D PAGE experiments and the use of PIP3 and H2O2 as well as small molecule inhibitors to respectively induce and inhibit NKp44L surface expression. Using plasmid encoding wild type or mutated form of p190 RhoGAP, we show that 3S mediated NKp44L surface expression on CD4(+) T cells is dependent on p190 RhoGAP. Finally, the role of TC10 in NKp44L surface induction was demonstrated by measuring Rho protein activity following 3S stimulation and using RNA interference. Thus, our results identify gC1qR as a new receptor of HIV-gp41 and demonstrate the signaling cascade it triggers. These findings identify potential mechanisms that new therapeutic strategies could use to prevent the CD4(+) T cell depletion during HIV infection and provide further evidence of a detrimental role played by NK cells in CD4(+) T cell depletion during HIV-1 infection.
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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.