ArticleMolecular pharmacology2010
Stimulation of the liver X receptor pathway inhibits HIV-1 replication via induction of ATP-binding cassette transporter A1.
Article in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Nef is a key player in neuroinflammation and myelin impairment associated with neuroHIV.Frontiers in neurology · 2025Article
- Review
- Extracellular vesicles produced by HIV-1 Nef-expressing cells induce myelin impairment and oligodendrocyte damage in the mouse central nervous system.Journal of neuroinflammation · 2024Article
- Review
- Lipid Raft Integrity and Cellular Cholesterol Homeostasis Are Critical for SARS-CoV-2 Entry into Cells.Nutrients · 2022Article
- Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts.mBio · 2020Article
- Associations of gender and serum total cholesterol with CD4+ T cell count and HIV RNA load in antiretroviral-naïve individuals in Addis Ababa.BMC public health · 2018Article
- Article
- Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease.Nutrients · 2018Review
- Liver X receptors link lipid metabolism and inflammation.FEBS letters · 2017Review
- Roles of the Mevalonate Pathway and Cholesterol Trafficking in Pulmonary Host Defense.Current molecular pharmacology · 2017Article
- The Intracellular Cholesterol Landscape: Dynamic Integrator of the Immune Response.Trends in immunology · 2016Review
- Interaction Between HIV-1 Nef and Calnexin: From Modeling to Small Molecule Inhibitors Reversing HIV-Induced Lipid Accumulation.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- N-Myc expression enhances the oncolytic effects of vesicular stomatitis virus in human neuroblastoma cells.Molecular therapy oncolytics · 2016Article
- Murine Norovirus Infection Variably Alters Atherosclerosis in Mice Lacking Apolipoprotein E.Comparative medicine · 2015Article
- Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pig-Tailed Macaques by Using a Systems Biology Approach.Journal of virology · 2015Article
- Stimulation of Liver X Receptor Has Potent Anti-HIV Effects in a Humanized Mouse Model of HIV Infection.The Journal of pharmacology and experimental therapeutics · 2015Article
- HIV-1 protein Nef inhibits activity of ATP-binding cassette transporter A1 by targeting endoplasmic reticulum chaperone calnexin.The Journal of biological chemistry · 2014Article
- Interaction of pathogens with host cholesterol metabolism.Current opinion in lipidology · 2014Review
- Cardiovascular Disease-Risk Markers in HIV Patients.Journal of AIDS & clinical research · 2014Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Cholesterol plays an important role in the HIV life cycle, and infectivity of cholesterol-depleted HIV virions is significantly impaired. Recently, we demonstrated that HIV-1, via its protein Nef, inhibits the activity of the major cellular cholesterol transporter ATP binding cassette transporter A1 (ABCA1), suggesting that the virus may use this mechanism to get access to cellular cholesterol. In this study, we investigated the effect on HIV infection of a synthetic liver X receptor (LXR) ligand, N-(2,2,2-trifluoro-ethyl)-N-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-benzenesulfonamide (TO-901317), which is a potent stimulator of ABCA1 expression. We demonstrate that TO-901317 restores cholesterol efflux from HIV-infected T lymphocytes and macrophages. TO-901317 potently suppressed HIV-1 replication in both cell types and inhibited HIV-1 replication in ex vivo cultured lymphoid tissue and in RAG-hu mice infected in vivo. This anti-HIV activity was dependent on ABCA1, because the effect of the drug was significantly reduced in ABCA1-defective T cells from a patient with Tangier disease, and RNA interference-mediated inhibition of ABCA1 expression eliminated the effect of TO-901317 on HIV-1 replication. TO-901317-mediated inhibition of HIV replication was due to reduced virus production and reduced infectivity of produced virions. The infectivity defect was in part due to reduced fusion activity of the virions, which was directly linked to reduced viral cholesterol. These results describe a novel approach to inhibiting HIV infection by stimulating ABCA1 expression.
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