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Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses.
Shaw, Andrew E; Hughes, Joseph; Gu, Quan; Behdenna, Abdelkader; Singer, Joshua B; Dennis, Tristan; Orton, Richard J; Varela, Mariana; Gifford, Robert J; Wilson, Sam J; Palmarini, Massimo.
Afiliação
  • Shaw AE; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Hughes J; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Gu Q; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Behdenna A; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Singer JB; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Dennis T; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Orton RJ; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Varela M; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Gifford RJ; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Wilson SJ; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Palmarini M; MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
PLoS Biol ; 15(12): e2004086, 2017 12.
Article em En | MEDLINE | ID: mdl-29253856
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interferon Tipo I / Fatores Reguladores de Interferon / Imunidade Inata / Mamíferos Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interferon Tipo I / Fatores Reguladores de Interferon / Imunidade Inata / Mamíferos Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article