ArticleEBioMedicine2016
HIV Nef- and Notch1-dependent Endocytosis of ADAM17 Induces Vesicular TNF Secretion in Chronic HIV Infection.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- A game of hide-and-seek: how extracellular vesicles evade the immune system.Drug delivery and translational research · 2025Review
- The Role of Extracellular Vesicles in Pandemic Viral Infections.Journal of microbiology (Seoul, Korea) · 2024Review
- HIV-1 release requires Nef-induced caspase activation.PloS one · 2023Article
- HIV-1 Nef Protein Affects Cytokine and Extracellular Vesicles Production in the GEN2.2 Plasmacytoid Dendritic Cell Line.Viruses · 2021Article
- Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid Formation.International journal of molecular sciences · 2021Article
- Viral Bad News Sent by EVAIL.Viruses · 2021Review
- Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction.Viruses · 2021Article
- Extracellular Vesicles as a New Promising Therapy in HIV Infection.Frontiers in immunology · 2021Review
- Review
- Review
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- A Disintegrin and Metalloproteinase-Control Elements in Infectious Diseases.Frontiers in cardiovascular medicine · 2020Review
- Multifunctional Roles of the N-Terminal Region of HIV-1Journal of virology · 2019Article
- Does HIV infection contribute to increased beta-amyloid synthesis and plaque formation leading to neurodegeneration and Alzheimer's disease?Journal of neurovirology · 2019Review
- Innate extracellular vesicles from melanoma patients suppress β-catenin in tumor cells by miRNA-34a.Life science alliance · 2019Article
- HIV-Nef Protein Persists in the Lungs of Aviremic Patients with HIV and Induces Endothelial Cell Death.American journal of respiratory cell and molecular biology · 2019Article
- Review
- Extracellular vesicles and chronic inflammation during HIV infection.Journal of extracellular vesicles · 2019Review
- Extracellular vesicles from mature dendritic cells (DC) differentiate monocytes into immature DC.Life science alliance · 2018Article
- HIV-1 Envelope Protein gp120 Promotes Proliferation and the Activation of Glycolysis in Glioma Cell.Cancers · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor (TNF) is a key cytokine in HIV replication and pathogenesis. For reasons that are not entirely clear, the cytokine remains upregulated despite anti-retroviral therapy (ART). Here we demonstrate that HIV Nef induces an alternative TNF secretion mechanism that remains active in chronic infection. Ingestion of Nef-containing plasma extracellular vesicles (pEV) from ART patients by primary immune cells, but also Nef expression, induced intracellular proTNF cleavage and secretion of vesicular TNF endosomes. Key event was the Nef-mediated routing of the TNF-converting enzyme ADAM17 into Rab4+ early endosomes and the Rab27+ secretory pathway. Analysis of lymph-node tissue by multi-epitope-ligand-cartography (MELC) confirmed a vesicular TNF secretion phenotype that co-localized with persistent Nef expression, and implicated Notch1 as an essential co-factor. Surprisingly Notch1 had no transcriptional effect but was required for the endosomal trafficking of ADAM17. We conclude that Nef expression and Nef-containing pEV mobilize TNF from endosomal compartments in acute and chronic infection.
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Registered trials
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.