TY - JOUR
T1 - ISG15
T2 - In Sickness and in Health
AU - Hermann, Mark
AU - Bogunovic, Dusan
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85006986748&partnerID=8YFLogxK
U2 - 10.1016/j.it.2016.11.001
DO - 10.1016/j.it.2016.11.001
M3 - Review article
C2 - 27887993
AN - SCOPUS:85006986748
SN - 1471-4906
VL - 38
SP - 79
EP - 93
JO - Trends in Immunology
JF - Trends in Immunology
IS - 2
ER -