ArticleProceedings of the National Academy of Sciences of the United States of America2005
HIV-1 Nef down-regulates the hemochromatosis protein HFE, manipulating cellular iron homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 91 citations in OpenAlex.
- Higher iron stores and the HFE 187C>G variant delay onset of peripheral neuropathy during combination antiretroviral therapy.PloS one · 2020Trial
- The role of iron in normal and impaired testicular function.Andrology · 2026Review
- Viruses hijack FPN1 to disrupt iron withholding and suppress host defense.Nature communications · 2025Article
- The kinase Bud32 regulates iron homeostasis in fungal pathogenFrontiers in immunology · 2025Article
- Human transferrin receptor can mediate SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Iron improves the antiviral activity of NK cells.Frontiers in immunology · 2024Article
- Contemporary Antiretroviral Therapy Dysregulates Iron Transport and Augments Mitochondrial Dysfunction in HIV-Infected Human Microglia and Neural-Lineage Cells.International journal of molecular sciences · 2023Article
- A cryo-electron microscopic approach to elucidate protein structures from human brain microsomes.Life science alliance · 2023Article
- Toward structural-omics of the bovine retinal pigment epithelium.Cell reports · 2022Article
- The beneficial role of Hepcidin peptide inhibitor in improved the symptoms of COVID-19 in diabetics: anti-inflammatory and potential therapeutic effects.Journal of diabetes and metabolic disorders · 2022Review
- Ferroptosis in viral infection: the unexplored possibility.Acta pharmacologica Sinica · 2022Review
- The Influence of Viral Infections on Iron Homeostasis and the Potential for Lactoferrin as a Therapeutic in the Age of the SARS-CoV-2 Pandemic.Nutrients · 2022Review
- HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response.Expert review of hematology · 2022Article
- Intracellular Low Iron Exerts Anti-BK Polyomavirus Effect by Inhibiting the Protein Synthesis of Exogenous Genes.Microbiology spectrum · 2021Article
- Higher CSF Ferritin Heavy-Chain (Fth1) and Transferrin Predict Better Neurocognitive Performance in People with HIV.Molecular neurobiology · 2021Observational
- Metabolic requirements of NK cells during the acute response against retroviral infection.Nature communications · 2021Article
- Understanding the Formation of Apoferritin Amyloid Fibrils.Biomacromolecules · 2021Article
- HIV Infection and Neurocognitive Disorders in the Context of Chronic Drug Abuse: Evidence for Divergent Findings Dependent upon Prior Drug History.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Review
- Ferritin: An Inflammatory Player Keeping Iron at the Core of Pathogen-Host Interactions.Microorganisms · 2020Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The multifunctional Nef protein of HIV-1 is important for the progression to AIDS. One action of Nef is to down-regulate surface MHC I molecules, helping infected cells to evade immunity. We found that Nef also down-regulates the macrophage-expressed MHC 1b protein HFE, which regulates iron homeostasis and is mutated in the iron-overloading disorder hemochromatosis. In model cell lines, Nef reroutes HFE to a perinuclear structure that overlaps the trans-Golgi network, causing a 90% reduction of surface HFE. This activity requires a Src-kinase-binding proline-rich domain of Nef and a conserved tyrosine-based motif in the cytoplasmic tail of HFE. HIV-1 infection of ex vivo macrophages similarly down-regulates naturally expressed surface HFE in a Nef-dependent manner. The effect of Nef expression on cellular iron was explored; iron and ferritin accumulation were increased in HIV-1-infected ex vivo macrophages expressing wild-type HFE, but this effect was lost with Nef-deleted HIV-1 or when infecting macrophages from hemochromatosis patients expressing mutated HFE. The iron accumulation in HIV-1-infected HFE-expressing macrophages was paralleled by an increase in cellular HIV-1-gag expression. We conclude that, through Nef and HFE, HIV-1 directly regulates cellular iron metabolism, possibly benefiting viral growth.
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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.