ArticleThe Journal of biological chemistry2014
HIV-1 protein Nef inhibits activity of ATP-binding cassette transporter A1 by targeting endoplasmic reticulum chaperone calnexin.
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 30 papers.
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
- Structural and functional modifications of neuronal lipid rafts: implications for HIV-associated neurological disorders.Journal of neuroinflammation · 2026Article
- HDL dysfunction: a role in the pathogenesis of cardiometabolic syndrome in chronic HIV infection?Metabolism: clinical and experimental · 2026Review
- Nef as a driver of immunodeficiency and HIV-associated diseases: insights from mouse models.Frontiers in immunology · 2026Review
- HIV-1 Nef synergizes with APOL1-G1 to induce nephrocyte cell death in HIV-related kidney diseases.Disease models & mechanisms · 2025Article
- Mechanisms of Immune Evasion in HIV-1: The Role of Virus-Host Protein Interactions.Current issues in molecular biology · 2025Review
- Analysis of Sigma-1 Receptor Antagonist BD1047 Effect on Upregulating Proteins in HIV-1-Infected Macrophages Exposed to Cocaine Using Quantitative Proteomics.Biomedicines · 2024Article
- Calnexin, More Than Just a Molecular Chaperone.Cells · 2023Review
- Role ofJournal of personalized medicine · 2022Review
- The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease.International journal of molecular sciences · 2021Review
- Direct interaction between ABCA1 and HIV-1 Nef: Molecular modeling and virtual screening for inhibitors.Computational and structural biotechnology journal · 2021Article
- HIV-1 Hijacking of Host ATPases and GTPases That Control Protein Trafficking.Frontiers in cell and developmental biology · 2021Review
- Comorbidities of HIV infection: role of Nef-induced impairment of cholesterol metabolism and lipid raft functionality.AIDS (London, England) · 2020Review
- Mechanistic Connections between Endoplasmic Reticulum (ER) Redox Control and Mitochondrial Metabolism.Cells · 2019Review
- Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells.PLoS pathogens · 2019Article
- Genome-wide association study (GWAS) of human host factors influencing viral severity of herpes simplex virus type 2 (HSV-2).Genes and immunity · 2019Article
- How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy.Frontiers in immunology · 2019Review
- Cholesterol efflux responds to viral load and CD4 counts in HIV+ patients and is dampened in HIV exposed.Journal of lipid research · 2018Article
- Modelling interaction between HIV-1 Nef and calnexin.AIDS (London, England) · 2018Article
- Intracellular and Plasma Membrane Events in Cholesterol Transport and Homeostasis.Journal of lipids · 2018Review
- Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
HIV-infected patients are at increased risk of developing atherosclerosis, in part due to an altered high density lipoprotein profile exacerbated by down-modulation and impairment of ATP-binding cassette transporter A1 (ABCA1) activity by the HIV-1 protein Nef. However, the mechanisms of this Nef effect remain unknown. Here, we show that Nef interacts with an endoplasmic reticulum chaperone calnexin, which regulates folding and maturation of glycosylated proteins. Nef disrupted interaction between calnexin and ABCA1 but increased affinity and enhanced interaction of calnexin with HIV-1 gp160. The Nef mutant that did not bind to calnexin did not affect the calnexin-ABCA1 interaction. Interaction with calnexin was essential for functionality of ABCA1, as knockdown of calnexin blocked the ABCA1 exit from the endoplasmic reticulum, reduced ABCA1 abundance, and inhibited cholesterol efflux; the same effects were observed after Nef overexpression. However, the effects of calnexin knockdown and Nef on cholesterol efflux were not additive; in fact, the combined effect of these two factors together did not differ significantly from the effect of calnexin knockdown alone. Interestingly, gp160 and ABCA1 interacted with calnexin differently; although gp160 binding to calnexin was dependent on glycosylation, glycosylation was of little importance for the interaction between ABCA1 and calnexin. Thus, Nef regulates the activity of calnexin to stimulate its interaction with gp160 at the expense of ABCA1. This study identifies a mechanism for Nef-dependent inactivation of ABCA1 and dysregulation of cholesterol metabolism.
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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.