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19 mai 2016
- doi: 10.1038/ncomms11496
- issn: 2041-1723
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info:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms11496
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info:eu-repo/semantics/altIdentifier/pmid/27193971
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info:eu-repo/semantics/altIdentifier/eissn/2041-1723
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_8158D3B3AE007
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
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S.D. Speer et al., « ISG15 deficiency and increased viral resistance in humans but not mice. », Serveur académique Lausannois, ID : 10.1038/ncomms11496
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ISG15 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.