Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses

Shaw, A. E. et al. (2017) Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses. PLoS Biology, 15(12), e2004086. (doi:10.1371/journal.pbio.2004086) (PMID:29253856) (PMCID:PMC574750)

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Abstract

The host innate immune response mediated by type I interferon (IFN) and the resulting up-regulation of hundreds of interferon-stimulated genes (ISGs) provide an immediate barrier to virus infection. Studies of the type I ‘interferome’ have mainly been carried out at a single species level, often lacking the power necessary to understand key evolutionary features of this pathway. Here, using a single experimental platform, we determined the properties of the interferomes of multiple vertebrate species and developed a webserver to mine the dataset. This approach revealed a conserved ‘core’ of 62 ISGs, including genes not previously associated with IFN, underscoring the ancestral functions associated with this antiviral host response. We show that gene expansion contributes to the evolution of the IFN system and that interferomes are shaped by lineage-specific pressures. Consequently, each mammal possesses a unique repertoire of ISGs, including genes common to all mammals and others unique to their specific species or phylogenetic lineages. An analysis of genes commonly down-regulated by IFN suggests that epigenetic regulation of transcription is a fundamental aspect of the IFN response. Our study provides a resource for the scientific community highlighting key paradigms of the type I IFN response.

Item Type:Articles
Keywords:General Biochemistry, Genetics and Molecular Biology, General Immunology and Microbiology, General Neuroscience, General Agricultural and Biological Sciences
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gifford, Dr Robert and Behdenna, Mr Abdelkader and Wilson, Dr Sam and Singer, Dr Joshua and Palmarini, Professor Massimo and Dennis, Tristan and Orton, Dr Richard and Shaw, Dr Andrew and Gu, Dr Quan and Hughes, Dr Joseph and Varela, Dr Mariana
Authors: Shaw, A. E., Hughes, J., Gu, Q., Behdenna, A., Singer, J. B., Dennis, T., Orton, R. J., Varela, M., Gifford, R. J., Wilson, S. J., and Palmarini, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Biology
Publisher:Public Library of Science
ISSN:1544-9173
ISSN (Online):1545-7885
Copyright Holders:Copyright © 2017 Shaw et al.
First Published:First published in PLoS Biology 15(12):e2004086
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
501441Centre for Integrated VirologyMassimo PalmariniMedical Research Council (MRC)G0801822MVLS III - CENTRE FOR VIRUS RESEARCH
618831Identifying and characterising antiretroviral interferon stimulated genes (ISGs)Sam WilsonMedical Research Council (MRC)MR/K024752/1MVLS III - CENTRE FOR VIRUS RESEARCH