Evidence map›Paper›PMID 23658454›Full record

ArticleJournal of virology2013

The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication.

Sinu P John, Christopher R Chin, Jill M Perreira, Eric M Feeley, Aaron M Aker, George Savidis, Sarah E Smith, Andrew E H Elia, Aaron R Everitt, Mehul Vora and 4 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

148 citing papers in PubMed, 182 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Innate Immune and Inflammatory Responses to Dengue Virus Infection.Current topics in microbiology and immunology · 2026
    Review
  9. Review
  10. Review
  11. Review
  12. IFITM1 and IFITM3 cooperate to restrict virus entry in endolysosomes.bioRxiv : the preprint server for biology · 2025
    Article
  13. Article
  14. mBio · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review

88 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Sinu P JohnDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Christopher R Chin
Jill M Perreira
Eric M Feeley
Aaron M Aker
George Savidis
Sarah E Smith
Andrew E H Elia
Aaron R Everitt
Mehul Vora
Thomas Pertel
Stephen J Elledge
Paul Kellam
Abraham L Brass
University of Massachusetts Chan Medical School · USRagon Institute of MGH, MIT and Harvard · USWellcome Sanger Institute · GBBrigham and Women's Hospital · USHarvard University · US

Funding

The Role of IFITM3 in the Anti-viral Host ResponseR01AI091786 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BRASS, ABRAHAM L · 2011 to 2015
$2.1M
Howard Hughes Medical InstituteNIAID NIH HHS 1R01AI091786NIAID NIH HHS R01 AI091786Wellcome Trust
6 · The paper itself

Abstract

The interferon-induced transmembrane protein 3 (IFITM3) gene is an interferon-stimulated gene that inhibits the replication of multiple pathogenic viruses in vitro and in vivo. IFITM3 is a member of a large protein superfamily, whose members share a functionally undefined area of high amino acid conservation, the CD225 domain. We performed mutational analyses of IFITM3 and identified multiple residues within the CD225 domain, consisting of the first intramembrane domain (intramembrane domain 1 [IM1]) and a conserved intracellular loop (CIL), that are required for restriction of both influenza A virus (IAV) and dengue virus (DENV) infection in vitro. Two phenylalanines within IM1 (F75 and F78) also mediate a physical association between IFITM proteins, and the loss of this interaction decreases IFITM3-mediated restriction. By extension, similar IM1-mediated associations may contribute to the functions of additional members of the CD225 domain family. IFITM3's distal N-terminal domain is also needed for full antiviral activity, including a tyrosine (Y20), whose alteration results in mislocalization of a portion of IFITM3 to the cell periphery and surface. Comparative analyses demonstrate that similar molecular determinants are needed for IFITM3's restriction of both IAV and DENV. However, a portion of the CIL including Y99 and R87 is preferentially needed for inhibition of the orthomyxovirus. Several IFITM3 proteins engineered with rare single-nucleotide polymorphisms demonstrated reduced expression or mislocalization, and these events were associated with enhanced viral replication in vitro, suggesting that possessing such alleles may impact an individual's risk for viral infection. On the basis of this and other data, we propose a model for IFITM3-mediated restriction.

Indexed as

Amino Acid SequenceAnimalsCell Culture TechniquesCloning, MolecularConserved SequenceDengue VirusDNA, ComplementaryDNA Mutational AnalysisDogsHEK293 CellsHeLa CellsHumansImmunoblottingImmunoprecipitationInfluenza A virusMadin Darby Canine Kidney CellsDNA, ComplementaryIFITM3 protein, humanMembrane ProteinsRNA-Binding Proteins

Identifiers

PMID23658454
PMCPMC3700195
OpenAlexW2001353863

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.