ISG15 deficiency and increased viral resistance in humans but not mice

DC ElementWertSprache
dc.contributor.authorSpeer, Scott D.
dc.contributor.authorLi, Zhi
dc.contributor.authorButa, Sofija
dc.contributor.authorPayelle-Brogard, Beatrice
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, Veronique
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.authorGarcia-Sastre, Adolfo
dc.contributor.authorPellegrini, Sandra
dc.contributor.authorBogunovic, Dusan
dc.date.accessioned2021-12-23T16:23:36Z-
dc.date.available2021-12-23T16:23:36Z-
dc.date.issued2016
dc.identifier.issn20411723
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/14597-
dc.description.abstractISG15 is an interferon (IFN)-alpha/beta-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-gamma-dependent antimycobacterial immunity, while free intracellular ISG15 is crucial for USP18-mediated downregulation of IFN-alpha/beta 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.
dc.description.sponsorshipNIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R00 AI106942-02, R01 AI101820, RO1 A1080672, R33 AI102267]; American Heart Association pre-doctoral fellowshipAmerican Heart Association; USPHS Institutional Research Training Award [T32-AI07647]; NRSAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32 AR07279-30]; Pew Scholar Award; DFGGerman Research Foundation (DFG)European Commission [SFB 944]; CRIP (Center for Research on Influenza Pathogenesis); NIAID Center of Excellence for Influenza Research and SurveillanceUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [HHSN272201400008C]; Institut PasteurEuropean Commission; CNRSCentre National de la Recherche Scientifique (CNRS)European Commission; INSERMInstitut National de la Sante et de la Recherche Medicale (Inserm)European Commission; Amgen Scholarship; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R00AI106942, R33AI102267, R01AI101820, T32AI007647] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [P30AR048335, T32AR007279] Funding Source: NIH RePORTER; This was supported in part by NIH grant R00 AI106942-02 to D.B., NIH grant R01 AI101820 to D.T., an American Heart Association pre-doctoral fellowship and a USPHS Institutional Research Training Award T32-AI07647 to T.J.G., NRSA T32 AR07279-30 to M.R.R., NIH grant RO1 A1080672 and Pew Scholar Award to D.J.L., funding by the DFG (SFB 944) to J.P., NIH grant R33 AI102267 to A.N.F. and B.L., CRIP (Center for Research on Influenza Pathogenesis), and NIAID funded Center of Excellence for Influenza Research and Surveillance (contract # HHSN272201400008C) to AGS. Experimental support was provided by the Speed Congenics Facility of the Rheumatic Disease Core Center (P30 AR048335). Work in the Cytokine Signaling Unit was supported by Institut Pasteur, CNRS, INSERM and an Amgen Scholarship to E.R.
dc.language.isoen
dc.publisherNATURE PUBLISHING GROUP
dc.relation.ispartofNATURE COMMUNICATIONS
dc.subject15-KDA PROTEIN
dc.subjectIN-VITRO
dc.subjectINFLUENZA-B VIRUS
dc.subjectINNATE ANTIVIRAL RESPONSE
dc.subjectINTERFERON-INDUCED PROTEINS
dc.subjectISOPEPTIDASE ACTIVITY
dc.subjectMOLECULAR CHARACTERIZATION
dc.subjectMultidisciplinary Sciences
dc.subjectNS1 PROTEIN
dc.subjectScience & Technology - Other Topics
dc.subjectSTIMULATED GENE 15
dc.subjectUBIQUITIN-LIKE PROTEIN
dc.titleISG15 deficiency and increased viral resistance in humans but not mice
dc.typejournal article
dc.identifier.doi10.1038/ncomms11496
dc.identifier.isiISI:000376089900001
dc.description.volume7
dc.contributor.orcid0000-0001-5837-7589
dc.contributor.orcid0000-0001-5837-7589
dc.contributor.orcid0000-0002-0564-8282
dc.contributor.orcid0000-0003-4422-4914
dc.contributor.orcid0000-0003-0760-1709
dc.contributor.orcid0000-0003-0961-3535
dc.contributor.orcid0000-0003-2077-6685
dc.contributor.orcid0000-0002-6551-1827
dc.contributor.orcid0000-0002-7325-4736
dc.contributor.orcid0000-0003-3677-1280
dc.contributor.orcid0000-0003-0838-8751
dc.contributor.researcheridY-6351-2019
dc.contributor.researcheridG-5546-2015
dc.contributor.researcheridG-6471-2017
dc.contributor.researcheridQ-4790-2018
dc.contributor.researcheridG-8735-2017
dc.contributor.researcheridA-8554-2016
dc.publisher.placeMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
dcterms.isPartOf.abbreviationNat. Commun.
dcterms.oaStatusGreen Published, Green Submitted, gold
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.orcid0000-0002-2143-2270-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidPiJa938-
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