ArticleRetrovirology2014
Lentiviral Nef suppresses iron uptake in a strain specific manner through inhibition of Transferrin endocytosis.
Article in Retrovirology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 53 citations in OpenAlex.
- HIV-1 manipulates CD96 on CD4Science advances · 2025Article
- Human transferrin receptor can mediate SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection.International journal of molecular sciences · 2023Article
- Lentiviral Nef Proteins Differentially Govern the Establishment of Viral Latency.Journal of virology · 2022Article
- HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response.Expert review of hematology · 2022Article
- Crossing the Iron Gate: Why and How Transferrin Receptors Mediate Viral Entry.Annual review of nutrition · 2018Review
- Dual role of the chromatin-binding factor PHF13 in the pre- and post-integration phases of HIV-1 replication.Open biology · 2017Article
- Harvesting pre-polarized macrophages using thermo-responsive substrates.Scientific reports · 2017Article
- AP-2 Is the Crucial Clathrin Adaptor Protein for CD4 Downmodulation by HIV-1 Nef in Infected Primary CD4+ T Cells.Journal of virology · 2015Article
- Short communication: high cellular iron levels are associated with increased HIV infection and replication.AIDS research and human retroviruses · 2015Article
- HIV-1 Nef and Vpu are functionally redundant broad-spectrum modulators of cell surface receptors, including tetraspanins.Journal of virology · 2014Article
- HIV-1 replication in human immune cells is independent of TAR DNA binding protein 43 (TDP-43) expression.PloS one · 2014Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreased cellular iron levels are associated with high mortality in HIV-1 infection. Moreover iron is an important cofactor for viral replication, raising the question whether highly divergent lentiviruses actively modulate iron homeostasis. Here, we evaluated the effect on cellular iron uptake upon expression of the accessory protein Nef from different lentiviral strains.
resultsSurface Transferrin receptor (TfR) levels are unaffected by Nef proteins of HIV-1 and its simian precursors but elevated in cells expressing Nefs from most other primate lentiviruses due to reduced TfR internalization. The SIV Nef-mediated reduction of TfR endocytosis is dependent on an N-terminal AP2 binding motif that is not required for downmodulation of CD4, CD28, CD3 or MHCI. Importantly, SIV Nef-induced inhibition of TfR endocytosis leads to the reduction of Transferrin uptake and intracellular iron concentration and is accompanied by attenuated lentiviral replication in macrophages.
conclusionInhibition of Transferrin and thereby iron uptake by SIV Nef might limit viral replication in myeloid cells. Furthermore, this new SIV Nef function could represent a virus-host adaptation that evolved in natural SIV-infected monkeys.
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