Skip to Main content Skip to Navigation
Journal articles

ISG15 deficiency and increased viral resistance in humans but not mice.

Scott Speer 1 Zhi Li 2 Sofija Buta 1 Béatrice Payelle-Brogard 2 Li Qian 1 Frédéric Vigant 1 Erminia Rubino 2 Thomas Gardner 1 Tim Wedeking 3 Mark Hermann 1 James Duehr 1 Ozden Sanal 4 Ilhan Tezcan 4 Nahal Mansouri 5 Payam Tabarsi 5 Davood Mansouri 5 Véronique Francois-Newton 2 Coralie Daussy 2 Marisela Rodriguez 6 Deborah Lenschow 6 Alexander Freiberg 7 Domenico Tortorella 1 Jacob Piehler 3 Benhur Lee 1 Adolfo García-Sastre 1 Sandra Pellegrini 2, * Dusan Bogunovic 1, *
* Corresponding author
1 MSSM - Icahn School of Medicine at Mount Sinai [New York]
2 Signalisation des Cytokines
3 Osnabrück University
4 Hacettepe University = Hacettepe Üniversitesi
5 SBUMS - Shahid Beheshti University of Medical Sciences [Tehran]
6 University of Washington School of Medicine
7 UTMB - The University of Texas Medical Branch
Abstract : ISG15 is an interferon (IFN)-a/b-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-g-dependent antimycobacterial immunity, while free intracellular ISG15 is crucial for USP18-mediated downregulation of IFN-a/b 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.
Document type :
Journal articles
Complete list of metadata

Cited literature [59 references]  Display  Hide  Download
https://hal-pasteur.archives-ouvertes.fr/pasteur-02070604
Contributor : Zhi Li <>
Submitted on : Monday, March 18, 2019 - 10:32:29 AM
Last modification on : Friday, April 3, 2020 - 9:54:15 AM
Long-term archiving on: : Wednesday, June 19, 2019 - 1:02:14 PM

File

Vignette du document
ncomms11496.pdf
Publication funded by an institution

Licence

Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

PASTEUR | CNRS

Citation

Scott Speer, Zhi Li, Sofija Buta, Béatrice Payelle-Brogard, Li Qian, et al.. ISG15 deficiency and increased viral resistance in humans but not mice.. Nature Communications, Nature Publishing Group, 2016, 7, pp.11496. ⟨10.1038/ncomms11496⟩. ⟨pasteur-02070604⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

260

Files downloads

436