ArticleJournal of molecular biology2022
Cholesterol Binds the Amphipathic Helix of IFITM3 and Regulates Antiviral Activity.
Article in Journal of molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Gene expression profiling of host lipid metabolism in SARS-CoV-2 infected patients: a systematic review and integrated bioinformatics analysis.BMC infectious diseases · 2024Pooled it
- The zinc metalloprotease ZMPSTE24 binds a distinct topological isoform of the tail-anchored protein IFITM3.The Journal of biological chemistry · 2026Article
- Interferon-induced transmembrane (IFITM) proteins at the tumour-immune interface: A four-axis framework for their context-dependent roles.Clinical and translational medicine · 2026Review
- Interferon-induced transmembrane proteins in cancer and virus biology: a membrane perspective.mBio · 2026Review
- Divergent HIV-1 Restriction Phenotypes of IFITMs Expressed in Target Cells and Incorporated into Virions.Biomolecules · 2026Article
- The zinc metalloprotease ZMPSTE24 binds a distinct topological isoform of the tail-anchored protein IFITM3.bioRxiv : the preprint server for biology · 2026Article
- IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits.Nature communications · 2026Article
- IFITM3 at the viral fusion-pore checkpoint: membrane energetics and entry-route-dependent outcomes.Frontiers in immunology · 2026Review
- Restriction of HIV-1 infectivity by interferon and IFITM3 is counteracted by Nef.Science advances · 2025Article
- IFITM1 as a modulator of surfaceome dynamics and aggressive phenotype in cervical cancer cells.Oncology reports · 2025Article
- Review
- IFITMs exhibit antiviral activity against Chikungunya and Zika virus infection via the alteration of TLRs and RLRs signaling pathways.Scientific reports · 2025Article
- Recent Advances in Stem Cells of Corneal Epithelia.Investigative ophthalmology & visual science · 2025Review
- Comprehensive Identification of Lipid-Membrane Protein Interactions via Advanced Proteomics and Extended Lipid-Immobilized Bead Technology.Analytical chemistry · 2025Article
- Attenuation of IFITM proteins' antiviral activity through sequestration into intraluminal vesicles of late endosomes.Frontiers in immunology · 2025Article
- Alternative splicing expands the antiviral IFITM repertoire in Chinese rufous horseshoe bats.PLoS pathogens · 2024Article
- SNARE mimicry by the CD225 domain of IFITM3 enables regulation of homotypic late endosome fusion.bioRxiv : the preprint server for biology · 2024Article
- Review
- The Antiviral Activity of Interferon-Induced Transmembrane Proteins and Virus Evasion Strategies.Viruses · 2024Review
- Influenza Virus Host Restriction Factors: The ISGs and Non-ISGs.Pathogens (Basel, Switzerland) · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The interferon-induced transmembrane (IFITM) proteins broadly inhibit the entry of diverse pathogenic viruses, including Influenza A virus (IAV), Zika virus, HIV-1, and SARS coronaviruses by inhibiting virus-cell membrane fusion. IFITM3 was previously shown to disrupt cholesterol trafficking, but the functional relationship between IFITM3 and cholesterol remains unclear. We previously showed that inhibition of IAV entry by IFITM3 is associated with its ability to promote cellular membrane rigidity, and these activities are functionally linked by a shared requirement for the amphipathic helix (AH) found in the intramembrane domain (IMD) of IFITM3. Furthermore, it has been shown that the AH of IFITM3 alters lipid membranes in vitro in a cholesterol-dependent manner. Therefore, we aimed to elucidate the relationship between IFITM3 and cholesterol in more detail. Using a fluorescence-based in vitro binding assay, we found that a peptide derived from the AH of IFITM3 directly interacted with the cholesterol analog, NBD-cholesterol, while other regions of the IFITM3 IMD did not, and native cholesterol competed with this interaction. In addition, recombinant full-length IFITM3 protein also exhibited NBD-cholesterol binding activity. Importantly, previously characterized mutations within the AH of IFITM3 that strongly inhibit antiviral function (F63Q and F67Q) disrupted AH structure in solution, inhibited cholesterol binding in vitro, and restricted bilayer insertion in silico. Our data suggest that direct interactions with cholesterol may contribute to the inhibition of membrane fusion pore formation by IFITM3. These findings may facilitate the design of therapeutic peptides for use in broad-spectrum antiviral therapy.
Indexed as
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.