{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T09:04:17Z","timestamp":1781427857262,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012763","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000}}],"reference-count":104,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"University of Edinburgh and Leiden University Medical Center One Health PhD Studentship"},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N013166\/1"],"award-info":[{"award-number":["MR\/N013166\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["Z23C010003"],"award-info":[{"award-number":["Z23C010003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science Foundation Research Fund for International Excellent Young Scientists","award":["RFIS-II, 82350610279"],"award-info":[{"award-number":["RFIS-II, 82350610279"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Species-specific interferon responses are shaped by the virus-host arms race. The human interferon-induced transmembrane protein (IFITM) family consists of three antiviral <jats:italic>IFITM<\/jats:italic> genes that arose by gene duplication. These genes restrict virus entry and are key players in antiviral interferon responses. The unique IFITM repertoires in different species influence their resistance to viral infections, but the role of IFITMs in shaping the enhanced antiviral immunity of reservoir bat species is unclear. Here, we identified an <jats:italic>IFITM<\/jats:italic> gene in Chinese rufous horseshoe bat, a natural host of severe acute respiratory syndrome (SARS)-related coronaviruses, that is alternatively spliced to produce two IFITM isoforms in native cells as shown by transcriptomics. These bat IFITMs have conserved structures <jats:italic>in vitro<\/jats:italic> as demonstrated by circular dichroism spectroscopy, yet they exhibit distinct antiviral specificities against influenza A virus, Nipah virus and coronaviruses including SARS-CoV, SARS-CoV-2 and MERS-CoV. In parallel with human IFITM1-3, bat IFITM isoforms localize to distinct sites of virus entry which influences their antiviral potency. Further bioinformatic analysis of IFITM repertoires in 206 mammals reveals that alternative splicing is a recurring strategy for IFITM diversification, albeit less widely adopted than gene duplication. These findings demonstrate that alternative splicing is a key strategy for evolutionary diversification in the IFITM family. Our study also highlights an example of convergent evolution where species-specific selection pressures led to expansion of the IFITM family through multiple means, underscoring the importance of IFITM diversity as a component of innate immunity.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012763","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T18:42:28Z","timestamp":1735238548000},"page":"e1012763","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Alternative splicing expands the antiviral IFITM repertoire in Chinese rufous horseshoe bats"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2597-6141","authenticated-orcid":true,"given":"Nelly S. 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K.","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin Kui","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengli","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Temperton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0196-1570","authenticated-orcid":true,"given":"Aaron T.","family":"Irving","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7508-4953","authenticated-orcid":true,"given":"Alex A.","family":"Compton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8973-1971","authenticated-orcid":true,"given":"Richard D.","family":"Sloan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"key":"ppat.1012763.ref001","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.3389\/fmicb.2018.03228","article-title":"IFITM Genes, Variants, and Their Roles in the Control and Pathogenesis of Viral Infections","volume":"9","author":"X Zhao","year":"2019","journal-title":"Front Microbiol"},{"key":"ppat.1012763.ref002","doi-asserted-by":"crossref","first-page":"e49265","DOI":"10.1371\/journal.pone.0049265","article-title":"Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates","volume":"7","author":"Z Zhang","year":"2012","journal-title":"PLoS 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with a new coronavirus of probable bat origin","author":"P Zhou","year":"2020","journal-title":"Nature"},{"key":"ppat.1012763.ref038","first-page":"14040","article-title":"Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats","author":"SK Lau","year":"2005","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ppat.1012763.ref039","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41586-022-04532-4","article-title":"Bat coronaviruses related to SARS-CoV-2 and infectious for human cells","author":"S Temmam","year":"2022","journal-title":"Nature"},{"key":"ppat.1012763.ref040","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41586-020-03128-0","article-title":"Lessons from the host defences of bats, a unique viral reservoir","author":"AT Irving","year":"2021","journal-title":"Nature"},{"key":"ppat.1012763.ref041","doi-asserted-by":"crossref","first-page":"104779","DOI":"10.1016\/j.isci.2022.104779","article-title":"Molecular, ecological, and behavioural drivers of the bat-virus relationship","author":"V Gonzalez","year":"2022","journal-title":"iScience"},{"key":"ppat.1012763.ref042","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1073\/pnas.1518240113","article-title":"Contraction of the type I IFN locus and unusual constitutive expression of IFN-\u03b1 in bats","volume":"113","author":"P Zhou","year":"2016","journal-title":"Proc Natl Acad Sci"},{"key":"ppat.1012763.ref043","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4049\/jimmunol.1701214","article-title":"The IFN Response in Bats Displays Distinctive IFN-Stimulated Gene Expression Kinetics with Atypical RNASEL Induction","volume":"200","author":"PC De La Cruz-Rivera","year":"2018","journal-title":"J 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Alghamdi","year":"2021","journal-title":"Genomics"},{"key":"ppat.1012763.ref058","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/infdis\/jix242","article-title":"Evaluation of IFITM3 rs12252 association with severe pediatric influenza infection","author":"AG Randolph","year":"2017","journal-title":"Journal of Infectious Diseases"},{"key":"ppat.1012763.ref059","doi-asserted-by":"crossref","first-page":"101202","DOI":"10.1016\/j.coviro.2022.101202","article-title":"Evolution of the interferon response: lessons from ISGs of diverse mammals","author":"MB McDougal","year":"2022","journal-title":"Current opinion in virology"},{"key":"ppat.1012763.ref060","doi-asserted-by":"crossref","first-page":"1213685","DOI":"10.3389\/fmicb.2023.1213685","article-title":"Evolution of primate interferon-induced transmembrane proteins (IFITMs): a story of gain and loss with a differentiation into a canonical cluster and IFITM retrogenes","author":"L Schelle","year":"2023","journal-title":"Frontiers in microbiology"},{"key":"ppat.1012763.ref061","first-page":"1","article-title":"Evolution of vertebrate interferon inducible transmembrane proteins","author":"D Hickford","year":"2012","journal-title":"BMC Genomics"},{"key":"ppat.1012763.ref062","article-title":"Homology-guided identification of a conserved motif linking the antiviral functions of IFITM3 to its oligomeric state","author":"K Rahman","year":"2020","journal-title":"eLife"},{"key":"ppat.1012763.ref063","first-page":"535","article-title":"Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor","author":"XY Ge","year":"2013","journal-title":"Nature"},{"key":"ppat.1012763.ref064","doi-asserted-by":"crossref","first-page":"e1001258","DOI":"10.1371\/journal.ppat.1001258","article-title":"Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus","author":"IC 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protein interferon-inducible transmembrane protein 3 (IFITM3) dually regulates its endocytosis and ubiquitination","author":"NM Chesarino","year":"2014","journal-title":"Journal of Biological Chemistry"},{"key":"ppat.1012763.ref069","doi-asserted-by":"crossref","first-page":"13697","DOI":"10.1128\/JVI.01828-12","article-title":"The N-terminal region of IFITM3 modulates its antiviral activity by regulating IFITM3 cellular localization","author":"R Jia","year":"2012","journal-title":"Journal of virology"},{"key":"ppat.1012763.ref070","article-title":"IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells","author":"J Lee","year":"2020","journal-title":"Nature"},{"key":"ppat.1012763.ref071","doi-asserted-by":"crossref","first-page":"e107821","DOI":"10.15252\/embj.2021107821","article-title":"TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells","author":"J Koch","year":"2021","journal-title":"The EMBO 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virus rescue system","volume":"103","author":"M Yoneda","year":"2006","journal-title":"Proc Natl Acad Sci"},{"key":"ppat.1012763.ref076","doi-asserted-by":"crossref","first-page":"D733","DOI":"10.1093\/nar\/gkv1189","article-title":"Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation","volume":"44","author":"NA O\u2019Leary","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ppat.1012763.ref077","article-title":"Reference-quality bat genomes illuminate adaptations to viral tolerance and disease resistance","author":"M Hiller","year":"2023","journal-title":"Research Square"},{"key":"ppat.1012763.ref078","doi-asserted-by":"crossref","first-page":"2246599","DOI":"10.1080\/22221751.2023.2246599","article-title":"The truncated IFITM3 facilitates the humoral immune response in inactivated influenza vaccine-vaccinated mice via interaction with CD81","author":"Q Xie","year":"2023","journal-title":"Emerging microbes & infections"},{"key":"ppat.1012763.ref079","article-title":"The short form of the zinc finger antiviral protein inhibits influenza a virus protein expression and is antagonized by the virus-encoded NS1","author":"Q Tang","year":"2017","journal-title":"Journal of virology"},{"key":"ppat.1012763.ref080","first-page":"697","article-title":"Alternative splicing as a source of phenotypic diversity","author":"Genetics","year":"2022","journal-title":"Nature reviews"},{"key":"ppat.1012763.ref081","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1471-2199-7-11","article-title":"Alternative first exon splicing regulates subcellular distribution of methionine sulfoxide reductases","author":"HY Kim","year":"2006","journal-title":"BMC molecular biology"},{"key":"ppat.1012763.ref082","first-page":"173","article-title":"Herpes simplex virus-1 induces expression of a novel MxA isoform that enhances viral replication","author":"CC Ku","year":"2011","journal-title":"Immunology and cell biology"},{"key":"ppat.1012763.ref083","doi-asserted-by":"crossref","first-page":"W29","DOI":"10.1093\/nar\/gkt282","article-title":"BLAST: a more efficient report with usability improvements","author":"GM Boratyn","year":"2013","journal-title":"Nucleic Acids Research"},{"key":"ppat.1012763.ref084","first-page":"W276","article-title":"Search and sequence analysis tools services from EMBL-EBI in 2022","author":"F Madeira","journal-title":"Nucleic acids research"},{"key":"ppat.1012763.ref085","author":"S. Andrews","year":"2010","journal-title":"FastQC \u2010 A quality control tool for high throughput sequence data"},{"key":"ppat.1012763.ref086","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ppat.1012763.ref087","first-page":"1438","article-title":"From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline","volume":"5","author":"Y Chen","year":"2016","journal-title":"F1000Res"},{"key":"ppat.1012763.ref088","first-page":"2101","article-title":"HELIQUEST: A web server to screen sequences with specific \u03b1-helical properties","author":"R Gautier","year":"2008","journal-title":"Bioinformatics (Oxford, England)"},{"key":"ppat.1012763.ref089","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkac345","article-title":"BeStSel: webserver for secondary structure and fold prediction for protein CD spectroscopy","author":"A Micsonai","year":"2022","journal-title":"Nucleic acids research"},{"key":"ppat.1012763.ref090","doi-asserted-by":"crossref","first-page":"12295","DOI":"10.1073\/pnas.200286297","article-title":"A conserved mechanism of retrovirus restriction in mammals","author":"G Towers","year":"2000","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ppat.1012763.ref091","article-title":"Analysis of antibody neutralisation activity against SARS-CoV-2 variants and seasonal human coronaviruses NL63, HKU1, and 229E induced by three different COVID-19 vaccine platforms","author":"D Cantoni","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"ppat.1012763.ref092","doi-asserted-by":"crossref","first-page":"1283113","DOI":"10.3389\/fpubh.2023.1283113","article-title":"Serological evidence of virus infection in Eidolon helvum fruit bats: implications for bushmeat consumption in Nigeria","volume":"11","author":"D Cantoni","year":"2023","journal-title":"Front Public Health"},{"key":"ppat.1012763.ref093","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jviromet.2008.10.012","article-title":"A one-step SYBR Green I-based product-enhanced reverse transcriptase assay for the quantitation of retroviruses in cell culture supernatants","author":"M Pizzato","year":"2009","journal-title":"Journal of virological methods"},{"key":"ppat.1012763.ref094","doi-asserted-by":"crossref","first-page":"e50859","DOI":"10.1371\/journal.pone.0050859","article-title":"Quantification of reverse transcriptase activity by real-time PCR as a fast and accurate method for titration of HIV, lenti- and retroviral vectors","author":"J Vermeire","year":"2012","journal-title":"PLoS One"},{"key":"ppat.1012763.ref095","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","author":"J Schindelin","year":"2012","journal-title":"Nature methods"},{"key":"ppat.1012763.ref096","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy","author":"S Bolte","year":"2006","journal-title":"Journal of microscopy"},{"key":"ppat.1012763.ref097","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular evolutionary genetics analysis across computing platforms","author":"S Kumar","year":"2018","journal-title":"Molecular Biology and Evolution"},{"key":"ppat.1012763.ref098","doi-asserted-by":"crossref","first-page":"W327","DOI":"10.1093\/nar\/gkh454","article-title":"CD-Search: protein domain annotations on the fly","author":"A Marchler-Bauer","year":"2004","journal-title":"Nucleic Acids Research"},{"key":"ppat.1012763.ref099","doi-asserted-by":"crossref","first-page":"D225","DOI":"10.1093\/nar\/gkq1189","article-title":"CDD: a conserved domain database for the functional annotation of proteins","author":"A Marchler-Bauer","year":"2011","journal-title":"Nucleic Acids Research"},{"key":"ppat.1012763.ref100","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/nar\/gkg020","article-title":"TMPDB: a database of experimentally-characterized transmembrane topologies","author":"M. Ikeda","year":"2003","journal-title":"Nucleic Acids Research"},{"key":"ppat.1012763.ref101","unstructured":"Rambaut A. FigTree \u2010 tree figure drawing tool, version 1.4.4. 2018. Available: http:\/\/tree.bio.ed.ac.uk\/"},{"key":"ppat.1012763.ref102","doi-asserted-by":"crossref","first-page":"D10","DOI":"10.1093\/nar\/gkaa892","article-title":"Database resources of the national center for biotechnology information","author":"EW Sayers","year":"2021","journal-title":"Nucleic acids research"},{"key":"ppat.1012763.ref103","article-title":"NCBI Taxonomy: a comprehensive update on curation, resources and tools","author":"CL Schoch","year":"2020","journal-title":"Database: the journal of biological databases and curation"},{"key":"ppat.1012763.ref104","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1189\/jlb.4A1014-483RR","article-title":"Limited specificity of IRF3 and ISGF3 in the transcriptional innate-immune response to double-stranded RNA","volume":"98","author":"DR Ourthiague","year":"2015","journal-title":"J Leukoc Biol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012763","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000}},{"DOI":"10.1371\/journal.ppat.1014001","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012763","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T19:07:20Z","timestamp":1738868840000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012763"}},"subtitle":[],"editor":[{"given":"Alexander E.","family":"Gorbalenya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,26]]},"references-count":104,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012763","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1012763","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,26]]}}}