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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
IFITM3 restricts the morbidity and mortality associated with influenza
Nature, Volume 484, No. 7395, Year 2012
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Description
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. © 2012 Macmillan Publishers Limited. All rights reserved.
Authors & Co-Authors
Clare, Simon
United Kingdom, London
Wellcome Trust
Pertel, Thomas
United States, Boston
Massachusetts General Hospital
Adams, David James
United Kingdom, London
Wellcome Trust
Goulding, David A.
United Kingdom, London
Wellcome Trust
Anttila, Verneri
United Kingdom, London
Wellcome Trust
Baillie, J. Kenneth
United Kingdom, Edinburgh
The University of Edinburgh
Walsh, Timothy Simon
United Kingdom, Edinburgh
The University of Edinburgh
Hume, David A.
United Kingdom, Edinburgh
The University of Edinburgh
Palotie, Aarno V.
United Kingdom, London
Wellcome Trust
Xue, Yali
United Kingdom, London
Wellcome Trust
Colonna, Vincenza
United Kingdom, London
Wellcome Trust
Italy, Rome
Consiglio Nazionale Delle Ricerche
Tyler-Smith, Chris
United Kingdom, London
Wellcome Trust
Dunning, Jake W.
United Kingdom, London
Imperial College London
Gordon, Stephen B.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Smyth, Rosalind L.
United Kingdom, Liverpool
Alder Hey Children's Hospital
Openshaw, Peter J.M.
United Kingdom, London
Imperial College London
Dougan, Gordon J.
United Kingdom, London
Wellcome Trust
Brass, Abraham L.
United States, Boston
Massachusetts General Hospital
Kellam, P.
United Kingdom, London
Wellcome Trust
United Kingdom, London
Medical Research Council
Everingham, Kirsty
Unknown Affiliation
Hope, David T.
Unknown Affiliation
Campbell, Archie I.
Unknown Affiliation
Kerr, Steven
Unknown Affiliation
Harrison, David A.
Unknown Affiliation
Rowan, Kathryn M.
Unknown Affiliation
Taylor, John C.
Unknown Affiliation
Taylor, Irene
Unknown Affiliation
Aldridge, Jerry R.
Unknown Affiliation
Richard, Christelle
Unknown Affiliation
Jardine, Claire M.
Unknown Affiliation
Rooney, Kevin Donal
Unknown Affiliation
Cairns, Charles B.
Unknown Affiliation
Hughes, Margaret A.
Unknown Affiliation
Gibson, J. P.
Unknown Affiliation
Murphy, Lee D.
Unknown Affiliation
Haley, Chris S.
Unknown Affiliation
Freeman, Tom C.
Unknown Affiliation
Chaussabel, Damien
Unknown Affiliation
Adamson, Walt E.
Unknown Affiliation
Carman, William F.
Unknown Affiliation
Zambon, Maria C.
Unknown Affiliation
Ashby, Deborah R.
Unknown Affiliation
Barclay, Wendy S.
Unknown Affiliation
Brett, Stephen J.
Unknown Affiliation
Cookson, William Osmond Charles M.
Unknown Affiliation
Drumright, Lydia N.
Unknown Affiliation
Gazzard, Brian G.
Unknown Affiliation
Griffiths, Mark J.D.
Unknown Affiliation
Hansel, Trevor T.
Unknown Affiliation
Herberg, Jethro Adam
Unknown Affiliation
Holmes, Alison Helen
Unknown Affiliation
Hussell, Tracy
Unknown Affiliation
Johnston, Sebastian Lennox
Unknown Affiliation
Kon, Onn Minn
Unknown Affiliation
Levin, Michael L.
Unknown Affiliation
Moffatt, Miriam F.
Unknown Affiliation
Nadel, Simon
Unknown Affiliation
Warner, John Oliver
Unknown Affiliation
Aston, Stephen J.
Unknown Affiliation
Hay, Alan J.
Unknown Affiliation
McCauley, John William
Unknown Affiliation
O’Garra, Anne
Unknown Affiliation
Banchereau, Jacques F.J.
Unknown Affiliation
Hayward, Andrew C.
Unknown Affiliation
Simmonds, Peter N.
Unknown Affiliation
McNamara, Paul Stephen
Unknown Affiliation
Semple, Malcolm Gracie
Unknown Affiliation
Nguyen-Van-Tam, Jonathan S.
Unknown Affiliation
Ho, Ling Pei
Unknown Affiliation
McMichael, Andrew James
Unknown Affiliation
Statistics
Citations: 577
Authors: 70
Affiliations: 9
Identifiers
Doi:
10.1038/nature10921
ISSN:
00280836
Research Areas
Genetics And Genomics
Study Design
Cross Sectional Study