ISG15 deficiency and increased viral resistance in humans but not mice
Autor(en): | Speer, Scott D. Li, Zhi Buta, Sofija Payelle-Brogard, Beatrice Qian, Li Vigant, Frederic Rubino, Erminia Gardner, Thomas J. Wedeking, Tim Hermann, Mark Duehr, James Sanal, Ozden Tezcan, Ilhan Mansouri, Nahal Tabarsi, Payam Mansouri, Davood Francois-Newton, Veronique Daussy, Coralie F. Rodriguez, Marisela R. Lenschow, Deborah J. Freiberg, Alexander N. Tortorella, Domenico Piehler, Jacob Lee, Benhur Garcia-Sastre, Adolfo Pellegrini, Sandra Bogunovic, Dusan |
Stichwörter: | 15-KDA PROTEIN; IN-VITRO; INFLUENZA-B VIRUS; INNATE ANTIVIRAL RESPONSE; INTERFERON-INDUCED PROTEINS; ISOPEPTIDASE ACTIVITY; MOLECULAR CHARACTERIZATION; Multidisciplinary Sciences; NS1 PROTEIN; Science & Technology - Other Topics; STIMULATED GENE 15; UBIQUITIN-LIKE PROTEIN | Erscheinungsdatum: | 2016 | Herausgeber: | NATURE PUBLISHING GROUP | Journal: | NATURE COMMUNICATIONS | Volumen: | 7 | Zusammenfassung: | ISG15 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. |
ISSN: | 20411723 | DOI: | 10.1038/ncomms11496 |
Zur Langanzeige
Seitenaufrufe
1
Letzte Woche
0
0
Letzter Monat
0
0
geprüft am 28.04.2024