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dc.contributor.authorCaddy, SL
dc.contributor.authorWang, Meng
dc.contributor.authorKrishnamurthy, Pramilla
dc.contributor.authorUttenthal, Ben
dc.contributor.authorChandra, Anita
dc.contributor.authorCrawley, Charles
dc.contributor.authorJames, Leo
dc.date.accessioned2018-01-19T18:45:45Z
dc.date.available2018-01-19T18:45:45Z
dc.date.issued2018-02-12
dc.identifier.issn1753-4259
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/270855
dc.description.abstractVirus infection is a major cause of morbidity and mortality following allogeneic haematopoietic stem cell transplant (HSCT), with up to 1 in 4 deaths directly linked to viral disease. Whilst awaiting lymphocyte reconstitution post HSCT, the innate anti-viral immune response is the first line of defence against invading viruses. Several novel innate viral sensing pathways have recently been characterized, but their physiological importance in humans is poorly understood. We analysed a panel of innate viral sensor genes in HSCT patients, and assessed whether differences in innate anti-viral responses could account for variation in susceptibility to viral infections. Expression levels of innate viral sensors in HSCT patients with active viral infections, HSCT patient without active infections, and healthy volunteers were highly homogenous. Although IFNα expression was upregulated in actively-infected patients relative to controls, a corresponding upregulation of innate viral sensor expression was not observed. IFNα stimulation of patient peripheral blood mononuclear cells (PBMCs) in-vitro showed intact IFNα signaling, but actively-infected patients’ PBMCs had reduced upregulation of innate viral sensors. We show that the aberrant IFNα responses in HSCT patients were not due to calcineurin inhibition. Our data therefore raises the possibility of an intrinsic defect in innate viral sensor upregulation in HSCT patients following viral infection.
dc.description.sponsorshipThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a Junior Research Fellowship to SLC from Magdalene College, Cambridge. This work was supported by the Medical Research Council MC_U105181010.
dc.publisherKarger
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjecthematopoetic stem cell transplant
dc.subjectinnate immune sensor
dc.subjectvirus
dc.titleCharacterisation of innate immune viral sensors in patients following allogeneic haematopoietic stem cell transplantation
dc.typeArticle
prism.publicationDate2018
prism.publicationNameInnate Immunity
dc.identifier.doi10.17863/CAM.17642
dcterms.dateAccepted2018-01-16
rioxxterms.versionofrecord10.1177/1753425918757898
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc/4.0/
rioxxterms.licenseref.startdate2018-02-12
dc.contributor.orcidWang, Sarah [0000-0002-9790-7420]
dc.contributor.orcidChandra, Anita [0000-0002-9061-879X]
dc.identifier.eissn1753-4267
rioxxterms.typeJournal Article/Review
cam.issuedOnline2018-02-12
cam.orpheus.successThu Jan 30 12:59:17 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial 4.0 International