ArticleThe Journal of biological chemistry2020
HIV-1 Nef dimers short-circuit immune receptor signaling by activating Tec-family kinases at the host cell membrane.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- HIV-1 Nef inhibits the JAK/STAT signaling pathway by inducing proteasomal degradation of STAT1.PloS one · 2026Article
- Nef defect attenuates HIV viremia and immune dysregulation in the bone marrow-liver-thymus-spleen (BLTS) humanized mouse model.Virology · 2024Article
- Neutron Reflectometry and Molecular Simulations Demonstrate HIV-1 Nef Homodimer Formation on Model Lipid Bilayers.Journal of molecular biology · 2023Article
- The HIV-1 protein Nef activates the Tec family kinase Btk by stabilizing an intermolecular SH3-SH2 domain interaction.Science signaling · 2022Article
- Inhibitors of HIV-1 Nef-Mediated Activation of the Myeloid Src-Family Kinase Hck Block HIV-1 Replication in Macrophages and Disrupt MHC-I Downregulation.ACS infectious diseases · 2022Article
- The BLT Humanized Mouse Model as a Tool for Studying Human Gamma Delta T Cell-HIV InteractionsFrontiers in immunology · 2022Article
- Visualization of Host Cell Kinase Activation by Viral Proteins Using GFP Fluorescence Complementation and Immunofluorescence Microscopy.Bio-protocol · 2021Article
- Nef homodimers down-regulate SERINC5 by AP-2-mediated endocytosis to promote HIV-1 infectivity.The Journal of biological chemistry · 2020Article
- Structure, function, and inhibitor targeting of HIV-1 Nef-effector kinase complexes.The Journal of biological chemistry · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The HIV-1 virulence factor Nef promotes high-titer viral replication, immune escape, and pathogenicity. Nef interacts with interleukin-2-inducible T-cell kinase (Itk) and Bruton's tyrosine kinase (Btk), two Tec-family kinases expressed in HIV-1 target cells (CD4 T cells and macrophages, respectively). Using a cell-based bimolecular fluorescence complementation assay, here we demonstrate that Nef recruits both Itk and Btk to the cell membrane and induces constitutive kinase activation in transfected 293T cells. Nef homodimerization-defective mutants retained their interaction with both kinases but failed to induce activation, supporting a role for Nef homodimer formation in the activation mechanism. HIV-1 infection up-regulates endogenous Itk activity in SupT1 T cells and donor-derived peripheral blood mononuclear cells. However, HIV-1 strains expressing Nef variants with mutations in the dimerization interface replicated poorly and were significantly attenuated in Itk activation. We conclude that direct activation of Itk and Btk by Nef at the membrane in HIV-infected cells may override normal immune receptor control of Tec-family kinase activity to enhance the viral life cycle.
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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 Socratic graph.