Skip to Main content Skip to Navigation
Journal articles

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

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
Contributor : Zhi Li Connect in order to contact the contributor
Submitted on : Monday, March 18, 2019 - 10:32:29 AM
Last modification on : Friday, August 5, 2022 - 2:33:52 PM
Long-term archiving on: : Wednesday, June 19, 2019 - 1:02:14 PM


Publication funded by an institution


Distributed under a Creative Commons Attribution 4.0 International License




Scott D 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⟩



Record views


Files downloads