IFITM3 restricts the morbidity and mortality associated with influenza
Aaron R. Everitt,Simon Clare,Thomas Pertel,Sinu P. John,Rachael S. Wash,Sarah E. Smith,Christopher R. Chin,Eric M. Feeley,Jennifer S. Sims,David J. Adams,Helen M. Wise,Leanne Kane,David Goulding,Paul Digard,Verneri Anttila,J Kenneth Baillie,Timothy S. Walsh,David A. Hume,Aarno Palotie,Yali Xue,Vincenza Colonna,Vincenza Colonna,Chris Tyler-Smith,Jake Dunning,Stephen B. Gordon,Rosalind L. Smyth,Peter J. M. Openshaw,Gordon Dougan,Abraham L. Brass,Abraham L. Brass,Paul Kellam,Paul Kellam +31 more
TLDR
Data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans.Abstract:
The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses. Both the magnitude and breadth of the IFITM proteins' in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 'Spanish' influenza. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans.read more
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Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.
TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.
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Evolution and ecology of influenza A viruses.
TL;DR: Wild aquatic bird populations have long been considered the natural reservoir for influenza A viruses with virus transmission from these birds seeding other avian and mammalian hosts, but recent studies in bats have suggested other reservoir species may also exist.
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Interferon-Stimulated Genes: A Complex Web of Host Defenses
TL;DR: This review begins by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production and describes ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the Jak-STAT pathway.
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SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.
Carly G. K. Ziegler,Samuel J. Allon,Sarah K. Nyquist,Ian M. Mbano,Vincent N. Miao,Constantine N. Tzouanas,Yuming Cao,Ashraf S. Yousif,Julia Bals,Blake M. Hauser,Blake M. Hauser,Jared Feldman,Jared Feldman,Christoph Muus,Christoph Muus,Marc H. Wadsworth,Samuel W. Kazer,Travis K. Hughes,Benjamin Doran,G. James Gatter,G. James Gatter,G. James Gatter,Marko Vukovic,Faith Taliaferro,Faith Taliaferro,Benjamin E. Mead,Zhiru Guo,Jennifer P. Wang,Delphine Gras,Magali Plaisant,Meshal Ansari,Ilias Angelidis,Heiko Adler,Jennifer M.S. Sucre,Chase J. Taylor,Brian M. Lin,Avinash Waghray,Vanessa Mitsialis,Vanessa Mitsialis,Daniel F. Dwyer,Kathleen M. Buchheit,Joshua A. Boyce,Nora A. Barrett,Tanya M. Laidlaw,Shaina L. Carroll,Lucrezia Colonna,Victor Tkachev,Victor Tkachev,Christopher W. Peterson,Christopher W. Peterson,Alison Yu,Alison Yu,Hengqi Betty Zheng,Hengqi Betty Zheng,Hannah P. Gideon,Caylin G. Winchell,Philana Ling Lin,Philana Ling Lin,Colin D. Bingle,Scott B. Snapper,Scott B. Snapper,Jonathan A. Kropski,Jonathan A. Kropski,Fabian J. Theis,Herbert B. Schiller,Laure-Emmanuelle Zaragosi,Pascal Barbry,Alasdair Leslie,Alasdair Leslie,Hans-Peter Kiem,Hans-Peter Kiem,JoAnne L. Flynn,Sarah M. Fortune,Sarah M. Fortune,Sarah M. Fortune,Bonnie Berger,Robert W. Finberg,Leslie S. Kean,Leslie S. Kean,Manuel Garber,Aaron G. Schmidt,Aaron G. Schmidt,Daniel Lingwood,Alex K. Shalek,Jose Ordovas-Montanes,Nicholas E. Banovich,Alvis Brazma,Tushar J. Desai,Thu Elizabeth Duong,Oliver Eickelberg,Christine S. Falk,Michael Farzan,Ian A. Glass,Muzlifah Haniffa,Peter Horvath,Deborah T. Hung,Naftali Kaminski,Mark A. Krasnow,Malte Kühnemund,Robert Lafyatis,Haeock Lee,Sylvie Leroy,Sten Linnarson,Joakim Lundeberg,Kerstin B. Meyer,Alexander V. Misharin,Martijn C. Nawijn,Marko Nikolic,Dana Pe'er,Joseph E. Powell,Stephen R. Quake,Jay Rajagopal,Purushothama Rao Tata,Emma L. Rawlins,Aviv Regev,Paul A. Reyfman,Mauricio Rojas,Orit Rosen,Kourosh Saeb-Parsy,Christos Samakovlis,Herbert B. Schiller,Joachim L. Schultze,Max A. Seibold,Douglas P. Shepherd,Jason R. Spence,Avrum Spira,Xin Sun,Sarah A. Teichmann,Fabian J. Theis,Alexander M. Tsankov,Maarten van den Berge,Michael von Papen,Jeffrey A. Whitsett,Ramnik J. Xavier,Yan Xu,Kun Zhang +135 more
TL;DR: The data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.
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Type I interferons in infectious disease.
TL;DR: Experimental models of tuberculosis have demonstrated that prostaglandin E2 and interleukin-1 inhibit type I IFN expression and its downstream effects, demonstrating that a cross-regulatory network of cytokines operates during infectious diseases to provide protection with minimum damage to the host.
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Journal Article
Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.
TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.
Journal ArticleDOI
Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.
TL;DR: The relationship between the two estimates of genetic variation at the DNA level, namely the number of segregating sites and the average number of nucleotide differences estimated from pairwise comparison, is investigated in this article.
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Gonçalo R. Abecasis,David Altshuler,David Altshuler,Adam Auton,Lisa D Brooks,Richard Durbin,Richard A. Gibbs,Matthew E. Hurles,Gil McVean +8 more
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