ArticlePLoS pathogens2008
HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP-dependent pathway in T cells.
Article in PLoS pathogens, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
What it found
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Who cites it
105 citing papers in PubMed, 143 citations in OpenAlex.
- HIV-1 Vpr Drives a B Cell-Like Phenotype in Primary CD4MedComm · 2026Article
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- Macrophage Immune Responses in Viral Infections: Functional Plasticity and Therapeutic Targeting.Journal of microbiology and biotechnology · 2026Review
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- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- HIV-1 manipulates CD96 on CD4Science advances · 2025Article
- Immune-mediated strategies to solving the HIV reservoir problem.Nature reviews. Immunology · 2025Review
- Adaptor Protein Complexes in HIV-1 Pathogenesis: Mechanisms and Therapeutic Potential.Viruses · 2025Review
- Mechanisms of Immune Evasion in HIV-1: The Role of Virus-Host Protein Interactions.Current issues in molecular biology · 2025Review
- Review
- Viral manipulation of the HLA class I antigen processing and presentation pathway.Frontiers in immunology · 2025Review
- State of the Field: Cytotoxic Immune Cell Responses inJournal of fungi (Basel, Switzerland) · 2024Review
- Article
- Exosomes multifunctional roles in HIV-1: insight into the immune regulation, vaccine development and current progress in delivery system.Frontiers in immunology · 2023Review
- Self-assembly and structure of a clathrin-independent AP-1:Arf1 tubular membrane coat.Science advances · 2022Article
- Plasma-Enabled Smart Nanoexosome Platform as Emerging Immunopathogenesis for Clinical Viral Infection.Pharmaceutics · 2022Review
- 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
- Modulation of Macrophage Polarization by Viruses: Turning Off/On Host Antiviral Responses.Frontiers in microbiology · 2022Review
- Article
- Quantitative visualization of endocytic trafficking through photoactivation of fluorescent proteins.Molecular biology of the cell · 2021Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I). To accomplish this, Nef binds to the cytoplasmic tails of both molecules and then, by mechanisms that are not well understood, disrupts the trafficking of each molecule in different ways. Specifically, Nef promotes CD4 internalization after it has been transported to the cell surface, whereas Nef uses the clathrin adaptor, AP-1, to disrupt normal transport of MHC-I from the TGN to the cell surface. Despite these differences in initial intracellular trafficking, we demonstrate that MHC-I and CD4 are ultimately found in the same Rab7(+) vesicles and are both targeted for degradation via the activity of the Nef-interacting protein, beta-COP. Moreover, we demonstrate that Nef contains two separable beta-COP binding sites. One site, an arginine (RXR) motif in the N-terminal alpha helical domain of Nef, is necessary for maximal MHC-I degradation. The second site, composed of a di-acidic motif located in the C-terminal loop domain of Nef, is needed for efficient CD4 degradation. The requirement for redundant motifs with distinct roles supports a model in which Nef exists in multiple conformational states that allow access to different motifs, depending upon which cellular target is bound by Nef.
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What OpenQuestion holds
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.