ArticleThe Journal of biological chemistry2014
Interaction of HIV-1 Nef protein with the host protein Alix promotes lysosomal targeting of CD4 receptor.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- 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
- An Amino Acid Polymorphism within the HIV-1 Nef Dileucine Motif Functionally Uncouples Cell Surface CD4 and SERINC5 Downregulation.Journal of virology · 2021Article
- Quantitative visualization of endocytic trafficking through photoactivation of fluorescent proteins.Molecular biology of the cell · 2021Article
- Human Respiratory Syncytial Virus Infection in a Human T Cell Line Is Hampered at Multiple Steps.Viruses · 2021Article
- Small molecule inhibitors targeting the PD-1/PD-L1 signaling pathway.Acta pharmacologica Sinica · 2021Review
- HIV-1 Hijacking of Host ATPases and GTPases That Control Protein Trafficking.Frontiers in cell and developmental biology · 2021Review
- Hijacking of endocytosis by HIV-1 Nef is becoming crystal clear.Nature structural & molecular biology · 2020Article
- Two Functional Variants of AP-1 Complexes Composed of either γ2 or γ1 Subunits Are Independently Required for Major Histocompatibility Complex Class I Downregulation by HIV-1 Nef.Journal of virology · 2020Article
- Ubiquitin E3 Ligase c-Cbl Is a Host Negative Regulator of Nef Protein of HIV-1.Frontiers in microbiology · 2020Article
- How HIV Nef Proteins Hijack Membrane Traffic To Promote Infection.Journal of virology · 2019Review
- The ESCRT-0 Protein HRS Interacts with the Human T Cell Leukemia Virus Type 2 Antisense Protein APH-2 and Suppresses Viral Replication.Journal of virology · 2019Article
- Plasma Membrane-Associated Restriction Factors and Their Counteraction by HIV-1 Accessory Proteins.Cells · 2019Review
- The autophagy protein ATG9A promotes HIV-1 infectivity.Retrovirology · 2019Article
- HIV and the Macrophage: From Cell Reservoirs to Drug Delivery to Viral Eradication.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Review
- HIP1R targets PD-L1 to lysosomal degradation to alter T cell-mediated cytotoxicity.Nature chemical biology · 2019Article
- HIV-1 Nef Antagonizes SERINC5 Restriction by Downregulation of SERINC5 via the Endosome/Lysosome System.Journal of virology · 2018Article
- ESCRT machinery components are required for Orthobunyavirus particle production in Golgi compartments.PLoS pathogens · 2018Article
- Viral effects on the content and function of extracellular vesicles.Nature reviews. Microbiology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Nef is an accessory protein of human immunodeficiency viruses that promotes viral replication and progression to AIDS through interference with various host trafficking and signaling pathways. A key function of Nef is the down-regulation of the coreceptor CD4 from the surface of the host cells. Nef-induced CD4 down-regulation involves at least two independent steps as follows: acceleration of CD4 endocytosis by a clathrin/AP-2-dependent pathway and targeting of internalized CD4 to multivesicular bodies (MVBs) for eventual degradation in lysosomes. In a previous work, we found that CD4 targeting to the MVB pathway was independent of CD4 ubiquitination. Here, we report that this targeting depends on a direct interaction of Nef with Alix/AIP1, a protein associated with the endosomal sorting complexes required for transport (ESCRT) machinery that assists with cargo recruitment and intraluminal vesicle formation in MVBs. We show that Nef interacts with both the Bro1 and V domains of Alix. Depletion of Alix or overexpression of the Alix V domain impairs lysosomal degradation of CD4 induced by Nef. In contrast, the V domain overexpression does not prevent cell surface removal of CD4 by Nef or protein targeting to the canonical ubiquitination-dependent MVB pathway. We also show that the Nef-Alix interaction occurs in late endosomes that are enriched in internalized CD4. Together, our results indicate that Alix functions as an adaptor for the ESCRT-dependent, ubiquitin-independent targeting of CD4 to the MVB pathway induced by Nef.
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Registered trials
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