ArticleThe EMBO journal2023
Interferon-inducible phospholipids govern IFITM3-dependent endosomal antiviral immunity.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 21 citations in OpenAlex.
- Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease.Haematologica · 2024Trial
- Interferon-induced transmembrane proteins in cancer and virus biology: a membrane perspective.mBio · 2026Review
- IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits.Nature communications · 2026Article
- BVDV utilizes PGC-1α downregulation to remodel the mitochondrial metabolic microenvironment, enhancing viral replication and impairing host immunity.Frontiers in veterinary science · 2026Article
- High-Throughput Metabolomics in Transfusion Medicine.Methods in molecular biology (Clifton, N.J.) · 2026Article
- IFITM3 at the viral fusion-pore checkpoint: membrane energetics and entry-route-dependent outcomes.Frontiers in immunology · 2026Review
- Interferon-induced transmembrane proteins: membrane gatekeepers of fusion and infection.Frontiers in cellular and infection microbiology · 2026Review
- Temporally integrated multiomics analysis elucidates intricate regulatory mechanisms of ASFV in a wild boar lung-derived clonal cell line.Veterinary research · 2025Article
- Early-life wheeze trajectories are associated with distinct asthma transcriptomes later in life.The Journal of allergy and clinical immunology · 2025Article
- Review
- Dynamic single-cell transcriptomic reveals the cellular heterogeneity and a novel fibroblast subpopulation in laryngotracheal stenosis.Biology direct · 2025Article
- PLSCR1 suppresses SARS-CoV-2 infection by downregulating cell surface ACE2.Journal of virology · 2025Article
- Restriction of Zika Virus Replication in Human Monocyte-Derived Macrophages by Pro-Inflammatory (M1) Polarization.International journal of molecular sciences · 2025Article
- Unraveled role of TLR7-mediated interferon signaling activation in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- Attenuation of IFITM proteins' antiviral activity through sequestration into intraluminal vesicles of late endosomes.Frontiers in immunology · 2025Article
- Innate immune control of influenza virus interspecies adaptation via IFITM3.Nature communications · 2024Article
- Review
- CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation.Circulation research · 2024Article
- The Antiviral Activity of Interferon-Induced Transmembrane Proteins and Virus Evasion Strategies.Viruses · 2024Review
- Red Blood Cells from Individuals with Lesch-Nyhan Syndrome: Multi-Omics Insights into a Novel S162N Mutation Causing Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency.Antioxidants (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interferon-induced transmembrane proteins (IFITM) are implicated in several biological processes, including antiviral defense, but their modes of action remain debated. Here, taking advantage of pseudotyped viral entry assays and replicating viruses, we uncover the requirement of host co-factors for endosomal antiviral inhibition through high-throughput proteomics and lipidomics in cellular models of IFITM restriction. Unlike plasma membrane (PM)-localized IFITM restriction that targets infectious SARS-CoV2 and other PM-fusing viral envelopes, inhibition of endosomal viral entry depends on lysines within the conserved IFITM intracellular loop. These residues recruit Phosphatidylinositol 3,4,5-trisphosphate (PIP3) that we show here to be required for endosomal IFITM activity. We identify PIP3 as an interferon-inducible phospholipid that acts as a rheostat for endosomal antiviral immunity. PIP3 levels correlated with the potency of endosomal IFITM restriction and exogenous PIP3 enhanced inhibition of endocytic viruses, including the recent SARS-CoV2 Omicron variant. Together, our results identify PIP3 as a critical regulator of endosomal IFITM restriction linking it to the Pi3K/Akt/mTORC pathway and elucidate cell-compartment-specific antiviral mechanisms with potential relevance for the development of broadly acting antiviral strategies.
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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.