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

Details

Serval ID
serval:BIB_8158D3B3AE00
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ISG15 deficiency and increased viral resistance in humans but not mice.
Journal
Nature communications
Author(s)
Speer S.D., Li Z., Buta S., Payelle-Brogard B., Qian L., Vigant F., Rubino E., Gardner T.J., Wedeking T., Hermann M., Duehr J., Sanal O., Tezcan I., Mansouri N., Tabarsi P., Mansouri D., Francois-Newton V., Daussy C.F., Rodriguez M.R., Lenschow D.J., Freiberg A.N., Tortorella D., Piehler J., Lee B., García-Sastre A., Pellegrini S., Bogunovic D.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
19/05/2016
Peer-reviewed
Oui
Volume
7
Pages
11496
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: epublish
Abstract
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
04/02/2021 19:53
Last modification date
07/07/2021 6:37
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