Interferon-Induced Protein 44 and Interferon-Induced Protein 44-Like Restrict Replication of Respiratory Syncytial Virus

Author:

Busse D. C.1ORCID,Habgood-Coote D.1,Clare S.2,Brandt C.2,Bassano I.1ORCID,Kaforou M.1ORCID,Herberg J.1ORCID,Levin M.1ORCID,Eléouët J.-F.3ORCID,Kellam P.14ORCID,Tregoning J. S.1ORCID

Affiliation:

1. Department of Infectious Disease, Imperial College London, St. Mary's Campus, London, United Kingdom

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

3. Unité De Virologie et Immunologie Moléculaires (UR892), INRA, Université Paris-Saclay, Jouy-en-Josas, France

4. Kymab Ltd., Cambridge, United Kingdom

Abstract

RSV infects all children under 2 years of age, but only a subset of children get severe disease. We hypothesize that susceptibility to severe RSV necessitating hospitalization in children without predefined risk factors is, in part, mediated at the antiviral gene level. However, there is a large array of antiviral genes, particularly in the ISG family, the mechanism of which is poorly understood. Having previously identified IFI44 and IFI44L as possible genes of interest in a bioinformatic screen, we dissected the function of these two genes in the control of RSV. Through a range of overexpression and knockout studies, we show that the genes are antiviral and antiproliferative. This study is important because IFI44 and IFI44L are upregulated after a wide range of viral infections, and IFI44L can serve as a diagnostic biomarker of viral infection.

Funder

Wellcome Trust

European Commission

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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