Evidence map›Paper›PMID 31826928›Full record

ArticleLife science alliance2020

Bat IFITM3 restriction depends on S-palmitoylation and a polymorphic site within the CD225 domain.

Camilla To Benfield, Farrell MacKenzie, Markus Ritzefeld, Michela Mazzon, Stuart Weston, Edward W Tate, Boon Han Teo, Sarah E Smith, Paul Kellam, Edward C Holmes and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Life science alliance, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

32 citing papers in PubMed, 45 citations in OpenAlex.

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  13. Antiviral effects of interferon-stimulated genes in bats.Frontiers in cellular and infection microbiology · 2023
    Review
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  15. Article
  16. ACS chemical biology · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Camilla To BenfieldDepartment of Pathobiology and Population Sciences, Royal Veterinary College, University of London, London, UK cbenfield@rvc.ac.uk.ORCID 0000-0001-7851-4181
Farrell MacKenzieMedical Research Council Laboratory for Molecular Cell Biology, University College London, London, UK.
Markus RitzefeldDepartment of Chemistry, Imperial College London, London, UK.
Michela MazzonMedical Research Council Laboratory for Molecular Cell Biology, University College London, London, UK.ORCID 0000-0002-2462-9925
Stuart WestonMedical Research Council Laboratory for Molecular Cell Biology, University College London, London, UK.
Edward W TateDepartment of Chemistry, Imperial College London, London, UK.ORCID 0000-0003-2213-5814
Boon Han TeoDepartment of Pathobiology and Population Sciences, Royal Veterinary College, University of London, London, UK.
Sarah E SmithKymab Ltd, The Bennet Building (B930), Babraham Research Campus, Cambridge, UK.
Paul KellamDepartment of Infectious Disease, Imperial College Faculty of Medicine, Wright Fleming Institute, St Mary's Campus, London, UK.ORCID 0000-0003-3166-4734
Edward C HolmesMarie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Mark MarshMedical Research Council Laboratory for Molecular Cell Biology, University College London, London, UK.ORCID 0000-0002-0213-3259
MRC Laboratory for Molecular Cell Biology · GBImperial College London · GBKymab (United Kingdom) · GBUniversity of London · GBThe University of Sydney · AU

Funding

Cancer Research UK 20183Cancer Research UK C29637/A20183Medical Research Council MC_U12266BMedical Research Council MC_UU_00012/1Medical Research Council MR/K015826/1Medical Research Council MR/M02492X/1
6 · The paper itself

Abstract

Host interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral restriction factors. Of these, IFITM3 potently inhibits viruses that enter cells through acidic endosomes, many of which are zoonotic and emerging viruses with bats (order Chiroptera) as their natural hosts. We previously demonstrated that microbat IFITM3 is antiviral. Here, we show that bat IFITMs are characterized by strong adaptive evolution and identify a highly variable and functionally important site-codon 70-within the conserved CD225 domain of IFITMs. Mutation of this residue in microbat IFITM3 impairs restriction of representatives of four different virus families that enter cells via endosomes. This mutant shows altered subcellular localization and reduced S-palmitoylation, a phenotype copied by mutation of conserved cysteine residues in microbat IFITM3. Furthermore, we show that microbat IFITM3 is S-palmitoylated on cysteine residues C71, C72, and C105, mutation of each cysteine individually impairs virus restriction, and a triple C71A-C72A-C105A mutant loses all restriction activity, concomitant with subcellular re-localization of microbat IFITM3 to Golgi-associated sites. Thus, we propose that S-palmitoylation is critical for Chiropteran IFITM3 function and identify a key molecular determinant of IFITM3 S-palmitoylation.

Indexed as

Polymorphism, GeneticA549 CellsAnimalsAntigens, DifferentiationChiropteraCodonEndosomesEvolution, MolecularHumansInfluenza A Virus, H1N1 SubtypeInfluenza, HumanLipoylationMembrane ProteinsPhylogenyProtein DomainsRNA-Binding ProteinsAntigens, DifferentiationCodonIFITM3 protein, humanleu-13 antigenMembrane ProteinsRNA-Binding Proteins

Identifiers

PMID31826928
PMCPMC6907390
OpenAlexW2994876269

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.