Type I interferon signaling, regulation and gene stimulation in chronic virus infection.


Princess Margaret Cancer Center, Tumor Immunotherapy Program, University Health Network, Toronto, Ontario, M5G 2M9, Canada; Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. Electronic address: [Email]


Type I Interferons (IFN-I) mediate numerous immune interactions during viral infections, from the establishment of an antiviral state to invoking and regulating innate and adaptive immune cells that eliminate infection. While continuous IFN-I signaling plays critical roles in limiting virus replication during both acute and chronic infections, sustained IFN-I signaling also leads to chronic immune activation, inflammation and, consequently, immune exhaustion and dysfunction. Thus, an understanding of the balance between the desirable and deleterious effects of chronic IFN-I signaling will inform our quest for IFN-based therapies for chronic viral infections as well as other chronic diseases, including cancer. As such the factors involved in induction, propagation and regulation of IFN-I signaling, from the initial sensing of viral nucleotides within the cell to regulatory downstream signaling factors and resulting IFN-stimulated genes (ISGs) have received significant research attention. This review summarizes recent work on IFN-I signaling in chronic infections, and provides an update on therapeutic approaches being considered to counter such infections.


Adaptive immunity,Chronic virus infection,Exhaustion,IRF,ISG,Immune response,Innate immunity,Interferon,Interferon regulatory factor,Interferon stimulatory gene,T cell,