title: ISG15: In Sickness and in Health.
abstract: ISG15 is a type I interferon (IFN)-inducible gene encoding a protein with pleiotropic functions, acting both as a soluble molecule and as a protein modifier. Surprisingly, and despite the antiviral functions of ISG15 described in mice, humans born with inactivating mutations of ISG15 do not present with any overt viral phenotype, but are highly susceptible to environmental mycobacteria and have autoinflammatory disease presentations. In vitro, ISG15 deficiency also leads to persistently high levels of type I IFN-stimulated gene expression and to increased resistance to all viruses tested to date. This suggests that ISG15 deficiency increases antiviral responses in humans, in stark contrast to expectations based on mouse experiments. We discuss here the roles of each of the forms of ISG15 in health and disease, as well as the differences between species.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, NY, NY 10029, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hermann
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, NY, NY 10029, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, NY, NY 10029, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, NY, NY 10029, USA. Electronic address: Dusan.Bogunovic@mssm.edu.
authors.forename: Dusan
authors.initials: D
authors.lastname: Bogunovic
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007109:Immunity; D007370:Interferon Type I / Q000235:genetics*; D051379:Mice; D009159:Mycobacteriaceae / Q000276:immunology*; D013045:Species Specificity; D014452:Ubiquitins / Q000235:genetics / Q000276:immunology*; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D014452:Ubiquitins; C074034:ISG15 protein, human