Selective inactivation of USP18 isopeptidase activity in vivo enhances ISG15 conjugation and viral resistance
Copyright policy )Selective inactivation of USP18 isopeptidase activity in vivo enhances ISG15 conjugation and viral resistance
Significance Viral infections still constitute a major health issue. Upon viral infection, interferon (IFN) elicits an antiviral response by activating multiple effector systems. The ubiquitin-like protein ISG15 is strongly induced by IFN and mediates its antiviral effect by being covalently conjugated to cellular and viral proteins. The protease USP18, which is also an important negative regulator of the IFN response, counteracts ISG15 conjugation. Within this study, we have generated knock-in mice expressing USP18, which selectively lacks protease activity. ISG15 modification was enhanced in these animals, but the IFN response was unaltered. This clearly shows that USP18 has enzymatic and nonenzymatic properties in vivo. Elevated ISGylation increased resistance to influenza B infections, qualifying USP18 protease inhibition as a potential antiviral strategy.
ISG15, UBP43, Medicina, Mice, Transgenic, Ubiquitin isopeptidase, Antiviral Agents, Influenza, Mice, Inbred C57BL, Influenza B virus, Mice, Drug Resistance, Viral, Interferon, Animals, Cytokines, Ubiquitin Thiolesterase, Ubiquitins, Cells, Cultured
ISG15, UBP43, Medicina, Mice, Transgenic, Ubiquitin isopeptidase, Antiviral Agents, Influenza, Mice, Inbred C57BL, Influenza B virus, Mice, Drug Resistance, Viral, Interferon, Animals, Cytokines, Ubiquitin Thiolesterase, Ubiquitins, Cells, Cultured
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