ArticleBlood advances2016
Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease.
Article in Blood advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
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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
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Does Sickle Cell Disease Protect against HIV Infection: A Systematic Review.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2022Pooled it
- 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
- Cell-Type-Specific Regulation of Ferroptosis in Atherosclerosis: Mechanisms and Therapeutic Potential of Natural Products.Cell biochemistry and function · 2026Review
- Can iron chelators ameliorate viral infections?Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
- Article
- Circulating Iron in Patients with Sickle Cell Disease Mediates the Release of Neutrophil Extracellular Traps.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2023Article
- Induction of Hepcidin Expression in the Renal Cortex of Sickle Cell Disease Mice.International journal of molecular sciences · 2023Article
- Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya.BMC cancer · 2023Article
- Iron Saturation Drives Lactoferrin Effects on Oxidative Stress and Neurotoxicity Induced by HIV-1 Tat.International journal of molecular sciences · 2023Article
- The role of ferroptosis in virus infections.Frontiers in microbiology · 2023Review
- HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response.Expert review of hematology · 2022Article
- Low transferrin levels predict heightened inflammation in patients with COVID-19: New insights.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2022Article
- Restriction of HIV-1 infection in sickle cell trait.Blood advances · 2021Article
- Endolysosome iron restricts Tat-mediated HIV-1 LTR transactivation by increasing HIV-1 Tat oligomerization and β-catenin expression.Journal of neurovirology · 2021Article
- Characterization of HIV risks in a Brazilian sickle cell disease population.BMC public health · 2020Article
- Review
- Article
- Article
- Depriving Iron Supply to the Virus Represents a Promising Adjuvant Therapeutic Against Viral Survival.Current clinical microbiology reports · 2020Review
- SARS-CoV-2 Infected Patient: from a Hematologist's Perspective.Mediterranean journal of hematology and infectious diseases · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1). HIV-1 inhibition was less pronounced in hepcidin-treated SCD PBMCs and more pronounced in the iron or iron chelators treated, suggesting a key role of iron metabolism. In SCD PBMCs, labile iron levels were reduced and protein levels of ferroportin, HIF-1α, IKBα, and HO-1 were increased. Hemin treatment induced ferroportin expression and inhibited HIV-1 in THP-1 cells, mimicking the HIV-1 inhibition in SCD PBMCs, especially as hepcidin similarly prevented HIV-1 inhibition. In THP-1 cells with knocked down ferroportin, IKBα, or HO-1 genes but not HIF-1α or p21, HIV-1 was not inhibited by hemin. Activity of SAMHD1-regulatory CDK2 was decreased, and SAMHD1 phosphorylation was reduced in SCD PBMCs and hemin-treated THP-1 cells, suggesting SAMHD1-mediated HIV-1 restriction in SCD. Our findings point to ferroportin as a trigger of HIV-1 restriction in SCD settings, linking reduced intracellular iron levels to the inhibition of CDK2 activity, reduction of SAMHD1 phosphorylation, increased IKBα expression, and inhibition of HIV-1 RT and transcription.
Identifiers
What OpenQuestion holds
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.