ISG15 deficiency and increased viral resistance in humans but not mice
| Autor: | Zhi Li, Benhur Lee, Ilhan Tezcan, Payam Tabarsi, Sofija Buta, Nahal Mansouri, Frederic Vigant, Domenico Tortorella, James Duehr, Béatrice Payelle-Brogard, Sandra Pellegrini, Li Qian, Scott D. Speer, Véronique Francois-Newton, Davood Mansouri, Jacob Piehler, Alexander N. Freiberg, Mark Hermann, Thomas J. Gardner, Marisela R. Rodriguez, Ozden Sanal, Tim Wedeking, Adolfo García-Sastre, Coralie F. Daussy, Deborah J. Lenschow, Erminia Rubino, Dusan Bogunovic |
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| Přispěvatelé: | Icahn School of Medicine at Mount Sinai [New York] (MSSM), Signalisation des Cytokines, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Osnabrück University, Hacettepe University = Hacettepe Üniversitesi, Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University, University of Washington School of Medicine, The University of Texas Medical Branch (UTMB), 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., Çocuk Sağlığı ve Hastalıkları, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universität Osnabrück - Osnabrück University |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Animals Cell Line Cytokines/genetics Cytokines/immunology Cytokines/metabolism Female Gene Expression Regulation Humans Interferons/metabolism Mice Primary Cell Culture Ubiquitin Thiolesterase/metabolism Ubiquitins/genetics Ubiquitins/immunology Ubiquitins/metabolism Virus Diseases/immunology Science General Physics and Astronomy Biology Viral resistance Viral infection General Biochemistry Genetics and Molecular Biology Article MESH: Primary Cell Culture 03 medical and health sciences MESH: Ubiquitins MESH: Animals MESH: Interferons MESH: Mice Ubiquitins MESH: Cytokines [SDV.GEN]Life Sciences [q-bio]/Genetics Multidisciplinary MESH: Humans General Chemistry MESH: Ubiquitin Thiolesterase ISG15 Virology MESH: Gene Expression Regulation 3. Good health MESH: Cell Line MESH: Virus Diseases 030104 developmental biology Virus Diseases Immunology [SDV.IMM]Life Sciences [q-bio]/Immunology Cytokines Interferons MESH: Female Ubiquitin Thiolesterase |
| Zdroj: | Nature communications, vol. 7, pp. 11496 Nature Communications Nature Communications, Nature Publishing Group, 2016, 7, pp.11496. ⟨10.1038/ncomms11496⟩ Nature Communications, Vol 7, Iss 1, Pp 1-10 (2016) Nature Communications, 2016, 7, pp.11496. ⟨10.1038/ncomms11496⟩ |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms11496⟩ |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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