Type I interferons regulate many biological processes, including the induction of an antiviral state, regulation of apoptosis, inhibition of cell growth, and modulation of both the innate and adaptive immune responses. Interferons mediate these activities through the induction of hundreds of gene products known as interferon-stimulated genes (ISGs). Work in the lab of Dr. Deborah Lenschow focuses on understanding the mechanism by which different ISGs function during viral infection and their relationship to disease. Recent work has focused on the ubiquitin-like protein ISG15. Mice lacking ISG15 display a dramatic increase in lethality following infection with multiple viruses. Ongoing work in the lab has focused on determining the mechanism by which ISG15 mediates these antiviral activities. Through the utilization of different viral models, this work has revealed the complexity of this pathway. In some models, ISG15 mediates its protection by modifying both host and viral proteins to inhibit replication. Using other viral models, the Lenschow lab has determined that ISG15 functions to limit immune pathology and damage induced to the host during viral infection by both conjugation-dependent and -independent mechanisms. Ongoing studies are further defining these novel activities of ISG15 as well as evaluating the therapeutic impact of increased ISG15 conjugation as an antiviral strategy. They are also characterizing novel IFN effector molecules and subtypes of IFN and evaluating the role of these proteins in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus.