ArticleBiochemistry2010
Mutation of the ATP cassette binding transporter A1 (ABCA1) C-terminus disrupts HIV-1 Nef binding but does not block the Nef enhancement of ABCA1 protein degradation.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Multiple Inhibitory Factors Act in the Late Phase of HIV-1 Replication: a Systematic Review of the Literature.Microbiology and molecular biology reviews : MMBR · 2018Pooled it
- An overview of the role of Niemann-pick C1 (NPC1) in viral infections and inhibition of viral infections through NPC1 inhibitor.Cell communication and signaling : CCS · 2023Review
- Extracellular vesicles carrying HIV-1 Nef induce long-term hyperreactivity of myeloid cells.Cell reports · 2022Article
- Role ofJournal of personalized medicine · 2022Review
- HIV-1-Mediated Acceleration of Oncovirus-Related Non-AIDS-Defining Cancers.Biomedicines · 2022Review
- Viral Bad News Sent by EVAIL.Viruses · 2021Review
- The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease.International journal of molecular sciences · 2021Review
- Article
- 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
- Genome-wide association study (GWAS) of human host factors influencing viral severity of herpes simplex virus type 2 (HSV-2).Genes and immunity · 2019Article
- Review
- Improving HIV proteome annotation: new features of BioAfrica HIV Proteomics Resource.Database : the journal of biological databases and curation · 2016Article
- Vascular smooth muscle cells contribute to APOL1-induced podocyte injury in HIV milieu.Experimental and molecular pathology · 2015Article
- Risk of coronary heart disease in patients with HIV infection.Nature reviews. Cardiology · 2014Review
- HIV-1 protein Nef inhibits activity of ATP-binding cassette transporter A1 by targeting endoplasmic reticulum chaperone calnexin.The Journal of biological chemistry · 2014Article
- Cardiovascular Disease-Risk Markers in HIV Patients.Journal of AIDS & clinical research · 2014Article
- The ABCA1 domain responsible for interaction with HIV-1 Nef is conformational and not linear.Biochemical and biophysical research communications · 2014Article
- Caveolin-1 reduces HIV-1 infectivity by restoration of HIV Nef mediated impairment of cholesterol efflux by apoA-I.Retrovirology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
HIV-1 infection and antiretroviral therapy are associated with a dyslipidemia marked by low levels of high-density lipoprotein and increased cardiovascular disease, but it is unclear whether virion replication plays a causative role in these changes. The HIV-1 Nef protein can impair ATP cassette binding transporter A1 (ABCA1) cholesterol efflux from macrophages, a potentially pro-atherosclerotic effect. This viral inhibition of efflux was correlated with a direct interaction between ABCA1 and Nef. Here, we defined the ABCA1 domain required for the Nef-ABCA1 protein-protein interaction and determined whether this interaction mediates the ability of Nef to downregulate ABCA1. Nef expressed in HEK 293 cells strongly inhibited ABCA1 efflux and protein levels but did not alter levels of cMIR, another transmembrane protein. Analysis of a panel of ABCA1 C-terminal mutants showed Nef binding required the ABCA1 C-terminal amino acids between positions 2225 and 2231. However, the binding of Nef to ABCA1 was not required for inhibition because the C-terminal ABCA1 mutants that did not bind Nef were still downregulated by Nef. Given this discordance, the mechanism of downregulation was investigated and was found to involve the acceleration of ABCA1 protein degradation but did not to depend upon the ABCA1 PEST sequence, which mediates the calpain proteolysis of ABCA1. Furthermore, it did not associate with a Nef-dependent induction of signaling through the unfolded protein response but was significantly dependent upon proteasomal function and could act on an ABCA1 mutant that fails to exit the endoplasmic reticulum. In summary, we show that Nef downregulates ABCA1 function by a post-translational mechanism that stimulates ABCA1 degradation but does not require the ability of Nef to bind ABCA1.
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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.