ArticleJournal of virology2007
Downregulation of CD4 by human immunodeficiency virus type 1 Nef is dependent on clathrin and involves direct interaction of Nef with the AP2 clathrin adaptor.
Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed, 225 citations in OpenAlex.
- Differential Ability of Primary HIV-1 Nef Isolates To Downregulate HIV-1 Entry Receptors.Journal of virology · 2015Trial
- Article
- Oncogenic Gα signaling requires AP-3-dependent recruitment to the endolysosomal compartment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A dileucine motif in TMEM163 is essential for its binding with both AP-3 and BLOC-1 complex.The Journal of biological chemistry · 2026Article
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- HIV-1 Nef inhibits the JAK/STAT signaling pathway by inducing proteasomal degradation of STAT1.PloS one · 2026Article
- HIV-1 Nef Uses a Conserved Pocket to Recruit the N-Terminal Cytoplasmic Tail of Serinc3.Viruses · 2025Article
- Restriction of HIV-1 infectivity by interferon and IFITM3 is counteracted by Nef.Science advances · 2025Article
- Mechanisms of Immune Evasion in HIV-1: The Role of Virus-Host Protein Interactions.Current issues in molecular biology · 2025Review
- Adaptor Protein Complexes in HIV-1 Pathogenesis: Mechanisms and Therapeutic Potential.Viruses · 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
- Rev-RRE activity modulates HIV-1 replication and latency reactivation: Implications for viral persistence and cure strategies.PLoS pathogens · 2025Article
- Characterization of Nanobody Binding to Distinct Regions of the SARS-CoV-2 Spike Protein by Flow Virometry.Viruses · 2025Article
- Kinetic investigation reveals an HIV-1 Nef-dependent increase in AP-2 recruitment and productivity at endocytic sites.Molecular biology of the cell · 2024Article
- HIV-1 Nef Changes the Proteome of T Cells Extracellular Vesicles Depleting IFITMs and Other Antiviral Factors.Molecular & cellular proteomics : MCP · 2023Article
- Article
- Patterns of human and porcine gammaherpesvirus-encoded BILF1 receptor endocytosis.Cellular & molecular biology letters · 2023Article
- Identification of 5' upstream sequence involved in HSPBP1 gene transcription and its downregulation during HIV-1 infection.Virus research · 2023Article
- Nef enhances HIV-1 replication and infectivity independently of SERINC5 in CEM T cells.Virology · 2023Article
- The adaptor protein chaperone AAGAB stabilizes AP-4 complex subunits.Molecular biology of the cell · 2022Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Nef, an accessory protein of human and simian immunodeficiency viruses, is a critical determinant of pathogenesis that promotes the progression from infection to AIDS. The pathogenic effects of Nef are in large part dependent on its ability to downregulate the macrophage and T-cell coreceptor, CD4. It has been proposed that Nef induces downregulation by linking the cytosolic tail of CD4 to components of the host-cell protein trafficking machinery. To identify these components, we developed a novel Nef-CD4 downregulation system in Drosophila melanogaster S2 cells. We found that human immunodeficiency virus type 1 (HIV-1) Nef downregulates human CD4 in S2 cells and that this process is subject to the same sequence requirements as in human cells. An RNA interference screen targeting protein trafficking genes in S2 cells revealed a requirement for clathrin and the clathrin-associated, plasma membrane-localized AP2 complex in the downregulation of CD4. The requirement for AP2 was confirmed in the human cell line HeLa. We also used a yeast three-hybrid system and glutathione S-transferase pull-down analyses to demonstrate a robust, direct interaction between HIV-1 Nef and AP2. This interaction requires a dileucine motif in Nef that is also essential for downregulation of CD4. Together, these results support a model in which HIV-1 Nef downregulates CD4 by promoting its accelerated endocytosis by a clathrin/AP2 pathway.
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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.