Genetic lesions of type I interferon signalling in human antiviral immunity

Christopher J.A. Duncan; Richard E. Randall; Sophie Hambleton

doi:10.1016/j.tig.2020.08.017

Genetic lesions of type I interferon signalling in human antiviral immunity

Christopher J.A. Duncan, Richard E. Randall, Sophie Hambleton

Research output: Contribution to journal › Review article › peer-review

Abstract

The concept that type I interferons (IFN-I) are essential to antiviral immunity derives from studies on animal models and cell lines. Virtually all pathogenic viruses have evolved countermeasures to IFN-I restriction, and genetic loss of viral IFN-I antagonists leads to virus attenuation. But just how important is IFN-I to antiviral defence in humans? The recent discovery of genetic defects of IFN-I signalling illuminates this and other questions of IFN biology, including the role of the mucosa-restricted type III IFNs (IFN-III), informing our understanding of the place of the IFN system within the concerted antiviral response. Here we review monogenic lesions of IFN-I signalling pathways and summarise the organising principles which emerge.

Original language	English
Pages (from-to)	46-58
Number of pages	13
Journal	Trends in Genetics
Volume	37
Issue number	1
Early online date	22 Sept 2020
DOIs	https://doi.org/10.1016/j.tig.2020.08.017
Publication status	Published - Jan 2021

Keywords

Type I interferons
Interferon-stimulated genes
JAK–STAT signalling
IFNAR
Inborn errors of immunity
Antiviral immunity

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10.1016/j.tig.2020.08.017Licence: CC BY

Duncan-2020-Genetic-lesions-of-Type-1-TiG-37-1-CCBY
Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 1.15 MBLicence: CC BY

Prof Randall Wellcome Trust: The interaction of paramyxoviruses with the interferon system
Randall, R. E. (PI)
The Wellcome Trust
1/04/14 → 31/03/20
Project: Standard

Cite this

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title = "Genetic lesions of type I interferon signalling in human antiviral immunity",

abstract = "The concept that type I interferons (IFN-I) are essential to antiviral immunity derives from studies on animal models and cell lines. Virtually all pathogenic viruses have evolved countermeasures to IFN-I restriction, and genetic loss of viral IFN-I antagonists leads to virus attenuation. But just how important is IFN-I to antiviral defence in humans? The recent discovery of genetic defects of IFN-I signalling illuminates this and other questions of IFN biology, including the role of the mucosa-restricted type III IFNs (IFN-III), informing our understanding of the place of the IFN system within the concerted antiviral response. Here we review monogenic lesions of IFN-I signalling pathways and summarise the organising principles which emerge.",

keywords = "Type I interferons, Interferon-stimulated genes, JAK–STAT signalling, IFNAR, Inborn errors of immunity, Antiviral immunity",

author = "Duncan, {Christopher J.A.} and Randall, {Richard E.} and Sophie Hambleton",

note = "Funding was provided by the Wellcome Trust [211153/Z/18/Z (C.J.A.D.), 207556/Z/17/Z (S.H.), 101788/Z/13/Z (R.E.R.)], Sir Jules Thorn Trust [12/JTA (S.H.)], and the British Medical Association (C.J.A.D).",

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AU - Duncan, Christopher J.A.

AU - Randall, Richard E.

AU - Hambleton, Sophie

N1 - Funding was provided by the Wellcome Trust [211153/Z/18/Z (C.J.A.D.), 207556/Z/17/Z (S.H.), 101788/Z/13/Z (R.E.R.)], Sir Jules Thorn Trust [12/JTA (S.H.)], and the British Medical Association (C.J.A.D).

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N2 - The concept that type I interferons (IFN-I) are essential to antiviral immunity derives from studies on animal models and cell lines. Virtually all pathogenic viruses have evolved countermeasures to IFN-I restriction, and genetic loss of viral IFN-I antagonists leads to virus attenuation. But just how important is IFN-I to antiviral defence in humans? The recent discovery of genetic defects of IFN-I signalling illuminates this and other questions of IFN biology, including the role of the mucosa-restricted type III IFNs (IFN-III), informing our understanding of the place of the IFN system within the concerted antiviral response. Here we review monogenic lesions of IFN-I signalling pathways and summarise the organising principles which emerge.

AB - The concept that type I interferons (IFN-I) are essential to antiviral immunity derives from studies on animal models and cell lines. Virtually all pathogenic viruses have evolved countermeasures to IFN-I restriction, and genetic loss of viral IFN-I antagonists leads to virus attenuation. But just how important is IFN-I to antiviral defence in humans? The recent discovery of genetic defects of IFN-I signalling illuminates this and other questions of IFN biology, including the role of the mucosa-restricted type III IFNs (IFN-III), informing our understanding of the place of the IFN system within the concerted antiviral response. Here we review monogenic lesions of IFN-I signalling pathways and summarise the organising principles which emerge.

KW - Type I interferons

KW - Interferon-stimulated genes

KW - JAK–STAT signalling

KW - IFNAR

KW - Inborn errors of immunity

KW - Antiviral immunity

U2 - 10.1016/j.tig.2020.08.017

DO - 10.1016/j.tig.2020.08.017

M3 - Review article

SN - 0168-9525

VL - 37

SP - 46

EP - 58

JO - Trends in Genetics

JF - Trends in Genetics

IS - 1

ER -

Genetic lesions of type I interferon signalling in human antiviral immunity

Abstract

Keywords

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Projects

Prof Randall Wellcome Trust: The interaction of paramyxoviruses with the interferon system

Cite this