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Lookup NU author(s): Dr Christopher Duncan,
Dr Siti Mohamad,
Professor Andrew Cant,
Dr Karin Engelhardt,
Professor Sophie Hambleton
This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Association for the Advancement of Science, 2015.
For re-use rights please refer to the publisher's terms and conditions.
Type I interferon (IFN-alpha/beta) is a fundamental antiviral defense mechanism. Mouse models have been pivotal to understanding the role of IFN-alpha/beta in immunity, although validation of these findings in humans has been limited. We investigated a previously healthy child with fatal encephalitis after inoculation of the live attenuated measles, mumps, and rubella (MMR) vaccine. By targeted resequencing, we identified a homozygous mutation in the high- affinity IFN-alpha/beta receptor (IFNAR2) in the proband, as well as a newborn sibling, that rendered cells unresponsive to IFN-alpha/beta. Reconstitution of the proband’s cells with wild-type IFNAR2 restored IFN-alpha/beta responsiveness and control of IFN-attenuated viruses. Despite the severe outcome of systemic live vaccine challenge, the proband had previously shown no evidence of heightened susceptibility to respiratory viral pathogens. The phenotype of IFNAR2 deficiency, together with similar findings in STAT2-deficient patients, supports an essential but narrow role for IFN-alpha/beta in human antiviral immunity.
Author(s): Duncan CJA, Mohamad SMB, Young DF, Skelton AJ, Leahy TR, Munday DC, Butler KM, Morfopoulou S, Brown JR, Hubank M, Connell J, Gavin PJ, McMahon C, Dempsey E, Lynch NE, Jacques TS, Valappil M, Cant AJ, Breuer J, Engelhardt KR, Randall RE, Hambleton S
Publication type: Article
Publication status: Published
Journal: Science Translational Medicine
Print publication date: 30/09/2015
Online publication date: 30/09/2015
Acceptance date: 24/07/2015
Date deposited: 26/10/2015
ISSN (print): 1946-6234
ISSN (electronic): 1946-6242
Publisher: American Association for the Advancement of Science
PubMed id: 26424569
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