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dc.contributor.authorSpeer, Scott D.
dc.contributor.authorLi, Zhi
dc.contributor.authorButa, Sofija
dc.contributor.authorPayelle-Brogard, Béatrice
dc.contributor.authorQian, Li
dc.contributor.authorVigant, Frederic
dc.contributor.authorRubino, Erminia
dc.contributor.authorGardner, Thomas J.
dc.contributor.authorWedeking, Tim
dc.contributor.authorHermann, Mark
dc.contributor.authorDuehr, James
dc.contributor.authorSanal, Ozden
dc.contributor.authorTezcan, Ilhan
dc.contributor.authorMansouri, Nahal
dc.contributor.authorTabarsi, Payam
dc.contributor.authorMansouri, Davood
dc.contributor.authorFrancois-Newton, Véronique
dc.contributor.authorDaussy, Coralie F.
dc.contributor.authorRodriguez, Marisela R.
dc.contributor.authorLenschow, Deborah J.
dc.contributor.authorFreiberg, Alexander N.
dc.contributor.authorTortorella, Domenico
dc.contributor.authorPiehler, Jacob
dc.contributor.authorLee, Benhur
dc.contributor.authorGarcía-Sastre, Adolfo
dc.contributor.authorPellegrini, Sandra
dc.contributor.authorBogunovic, Dusan
dc.date.accessioned2019-12-10T10:39:20Z
dc.date.available2019-12-10T10:39:20Z
dc.date.issued2016
dc.identifier.issn2041-1723
dc.identifier.urihttps://doi.org/10.1038/ncomms11496
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873964/
dc.identifier.urihttp://hdl.handle.net/11655/14115
dc.description.abstractISG15 is an interferon (IFN)-α/β-induced ubiquitin-like protein. It exists as a free molecule, intracellularly and extracellularly, and conjugated to target proteins. Studies in mice have demonstrated a role for Isg15 in antiviral immunity. By contrast, human ISG15 was shown to have critical immune functions, but not in antiviral immunity. Namely, free extracellular ISG15 is crucial in IFN-γ-dependent antimycobacterial immunity, while free intracellular ISG15 is crucial for USP18-mediated downregulation of IFN-α/β signalling. Here we describe ISG15-deficient patients who display no enhanced susceptibility to viruses in vivo, in stark contrast to Isg15-deficient mice. Furthermore, fibroblasts derived from ISG15-deficient patients display enhanced antiviral protection, and expression of ISG15 attenuates viral resistance to WT control levels. The species-specific gain-of-function in antiviral immunity observed in ISG15 deficiency is explained by the requirement of ISG15 to sustain USP18 levels in humans, a mechanism not operating in mice., ISG15 is a ubiquitin-like protein which has important immune-related functions in mice and humans. Here the authors demonstrate that, unlike in mice, human ISG15 stabilizes UPS18 and that ISG15-deficient human cells are more resistant to viral infection.
dc.relation.isversionof10.1038/ncomms11496
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleIsg15 Deficiency and Increased Viral Resistance in Humans but Not Mice
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalNature Communications
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları
dc.identifier.volume7
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus


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