ArticleThe EMBO journal2021
Opposing activities of IFITM proteins in SARS-CoV-2 infection.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
182 citing papers in PubMed, 3 syntheses or guidelines pooled it, 235 citations in OpenAlex.
- Single-cell analysis of adult human heart across healthy and cardiovascular disease patients reveals the cellular landscape underlying SARS-CoV-2 invasion of myocardial tissue through ACE2.Journal of translational medicine · 2023Pooled it
- Pooled it
- Interferon-induced transmembrane protein 3 gene polymorphisms are associated with COVID-19 susceptibility and severity: A meta-analysis.The Journal of infection · 2022Pooled it
- The zinc metalloprotease ZMPSTE24 binds a distinct topological isoform of the tail-anchored protein IFITM3.The Journal of biological chemistry · 2026Article
- Temperature-dependent replication and sensitivity to innate immunity of human coronavirus HKU1.Nature communications · 2026Article
- Temporal Dynamics of Innate Immune Activation and Viral Interference During Sequential Co-Infection with Influenza A Virus and SARS-CoV-2: Molecular Mechanisms, Clinical Evidence, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Comparative Transcriptomic Profiling Reveals Differences in Initiation of Antiviral Response in Low rAAV Producing HEK293 Suspension Cells.Biotechnology journal · 2026Article
- Polystyrene Microplastic-Induced Cellular Alterations and Their Effects on Viral Entry (RSV, HCoV-OC43, EV-A71) and Viral Persistence.Environment & health (Washington, D.C.) · 2026Article
- Article
- Redundant and distinct mechanisms suppress innate immune activation during SARS-CoV-2 infection.PLoS biology · 2026Article
- TNF inhibits SARS-CoV-2 induced cell-cell fusion through activating the SDC4-RhoA signaling to promote actin bundles formation.Cell insight · 2026Article
- COVID-19, the disease that changed the world.Medicine and pharmacy reports · 2026Review
- The zinc metalloprotease ZMPSTE24 binds a distinct topological isoform of the tail-anchored protein IFITM3.bioRxiv : the preprint server for biology · 2026Article
- Signal peptidase complex mediates rotavirus VP7 processing and virion assembly.PLoS pathogens · 2026Article
- Review
- IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits.Nature communications · 2026Article
- Host Responses to SARS-CoV-2 with an Emphasis on Cytokines.International journal of molecular sciences · 2026Review
- Rewriting the viral script: post-translational modifications orchestrating SARS-CoV-2 pathogenesis and immune evasion.Frontiers in microbiology · 2026Review
- 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
122 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Interferon-induced transmembrane proteins (IFITMs) restrict infections by many viruses, but a subset of IFITMs enhance infections by specific coronaviruses through currently unknown mechanisms. We show that SARS-CoV-2 Spike-pseudotyped virus and genuine SARS-CoV-2 infections are generally restricted by human and mouse IFITM1, IFITM2, and IFITM3, using gain- and loss-of-function approaches. Mechanistically, SARS-CoV-2 restriction occurred independently of IFITM3 S-palmitoylation, indicating a restrictive capacity distinct from reported inhibition of other viruses. In contrast, the IFITM3 amphipathic helix and its amphipathic properties were required for virus restriction. Mutation of residues within the IFITM3 endocytosis-promoting YxxФ motif converted human IFITM3 into an enhancer of SARS-CoV-2 infection, and cell-to-cell fusion assays confirmed the ability of endocytic mutants to enhance Spike-mediated fusion with the plasma membrane. Overexpression of TMPRSS2, which increases plasma membrane fusion versus endosome fusion of SARS-CoV-2, attenuated IFITM3 restriction and converted amphipathic helix mutants into infection enhancers. In sum, we uncover new pro- and anti-viral mechanisms of IFITM3, with clear distinctions drawn between enhancement of viral infection at the plasma membrane and amphipathicity-based mechanisms used for endosomal SARS-CoV-2 restriction.
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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.