ArticleMolecular biology of the cell2010
Small molecule inhibition of HIV-1-induced MHC-I down-regulation identifies a temporally regulated switch in Nef action.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 67 citations in OpenAlex.
- PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2.Communications biology · 2026Article
- Nef as a driver of immunodeficiency and HIV-associated diseases: insights from mouse models.Frontiers in immunology · 2026Review
- HIV-1 Nef activates proviral DNA transcription by recruiting Src kinase to phosphorylate host protein Nef-associated factor 1 to compromise its viral restrictive function.Journal of virology · 2025Article
- Mechanisms of Immune Evasion in HIV-1: The Role of Virus-Host Protein Interactions.Current issues in molecular biology · 2025Review
- Association between HIV-1 Nef-mediated MHC-I downregulation and the maintenance of the replication-competent latent viral reservoir in individuals with virally suppressed HIV-1 in Uganda: an exploratory cohort study.The Lancet. Microbe · 2025Article
- Recognition of HIV-1-infected fibrocytes lacking Nef-mediated HLA-B downregulation by HIV-1-specific T cells.Journal of virology · 2024Article
- Nef enhances HIV-1 replication and infectivity independently of SERINC5 in CEM T cells.Virology · 2023Article
- Review
- The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells.The Journal of clinical investigation · 2022Article
- Detection of the HIV-1 Accessory Proteins Nef and Vpu by Flow Cytometry Represents a New Tool to Study Their Functional Interplay within a Single Infected CD4Journal of virology · 2022Article
- Direct interaction between ABCA1 and HIV-1 Nef: Molecular modeling and virtual screening for inhibitors.Computational and structural biotechnology journal · 2021Article
- Structure, function, and inhibitor targeting of HIV-1 Nef-effector kinase complexes.The Journal of biological chemistry · 2020Review
- Host and Viral Factors Influencing Interplay between the Macrophage and HIV-1.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Review
- Lovastatin Inhibits HIV-1-Induced MHC-I Downregulation by Targeting Nef-AP-1 Complex Formation: A New Strategy to Boost Immune Eradication of HIV-1 Infected Cells.Frontiers in immunology · 2019Article
- Remodeling of HIV-1 Nef Structure by Src-Family Kinase Binding.Journal of molecular biology · 2018Article
- A single β-octyl glucoside molecule induces HIV-1 Nef dimer formation in the absence of partner protein binding.PloS one · 2018Article
- HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure.AIDS research and therapy · 2017Review
- Caught in the act - protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease.Journal of cell science · 2017Review
- HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling.Scientific reports · 2016Article
- PACS-2 mediates the ATM and NF-κB-dependent induction of anti-apoptotic Bcl-xL in response to DNA damage.Cell death and differentiation · 2016Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
HIV-1 Nef triggers down-regulation of cell-surface MHC-I by assembling a Src family kinase (SFK)-ZAP-70/Syk-PI3K cascade. Here, we report that chemical disruption of the Nef-SFK interaction with the small molecule inhibitor 2c blocks assembly of the multi-kinase complex and represses HIV-1-mediated MHC-I down-regulation in primary CD4(+) T-cells. 2c did not interfere with the PACS-2-dependent trafficking of Nef required for the Nef-SFK interaction or the AP-1 and PACS-1-dependent sequestering of internalized MHC-I, suggesting the inhibitor specifically interfered with the Nef-SFK interaction required for triggering MHC-I down-regulation. Transport studies revealed Nef directs a highly regulated program to down-regulate MHC-I in primary CD4(+) T-cells. During the first two days after infection, Nef assembles the 2c-sensitive multi-kinase complex to trigger down-regulation of cell-surface MHC-I. By three days postinfection Nef switches to a stoichiometric mode that prevents surface delivery of newly synthesized MHC-I. Pharmacologic inhibition of the multi-kinase cascade prevents the Nef-dependent block in MHC-I transport, suggesting the signaling and stoichiometric modes are causally linked. Together, these studies resolve the seemingly controversial models that describe Nef-induced MHC-I down-regulation and provide new insights into the mechanism of Nef action.
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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.