Interferon-Induced Transmembrane Protein 1 Restricts Replication of Viruses That Enter Cells via the Plasma Membrane

Author:

Smith S. E.12,Busse D. C.3ORCID,Binter S.12,Weston S.4,Diaz Soria C.1,Laksono B. M.5,Clare S.1,Van Nieuwkoop S.5,Van den Hoogen B. G.5,Clement M.6,Marsden M.6,Humphreys I. R.6,Marsh M.4,de Swart R. L.5ORCID,Wash R. S.12,Tregoning J. S.3ORCID,Kellam P.132

Affiliation:

1. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom

2. Kymab Ltd., Babraham Research Campus, Cambridge, United Kingdom

3. Mucosal Infection and Immunity Group, Section of Virology, Imperial College London, St. Mary’s Campus, London, United Kingdom

4. MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom

5. Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands

6. Division of Infection and Immunity/Systems Immunity University Research Institute, Cardiff University, Cardiff, United Kingdom

Abstract

Host susceptibility to viral infection is multifactorial, but early control of viruses not previously encountered is predominantly mediated by the interferon-stimulated gene (ISG) family. There are upwards of 300 of these genes, the majority of which do not have a clearly defined function or mechanism of action. The cellular location of these proteins may have an important effect on their function. One ISG located at the plasma membrane is interferon-inducible transmembrane protein 1 (IFITM1). Here we demonstrate that IFITM1 can inhibit infection with a range of viruses that enter via the plasma membrane. Mutant IFITM1 proteins that were unable to localize to the plasma membrane did not restrict viral infection. We also observed for the first time that IFITM1 plays a role in vivo , and Ifitm1 −/− mice were more susceptible to viral lung infection. These data contribute to our understanding of how ISGs prevent viral infections.

Funder

The Wellcome Trust

RCUK | Biotechnology and Biological Sciences Research Council

RCUK | Medical Research Council

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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