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

• Published in: Seminars in immunology Vol. 43; p. 101277
• Main Authors: Lukhele, Sabelo, Boukhaled, Giselle M., Brooks, David G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2019
• Subjects: Adaptive immunity; Animals; Chronic Disease; Chronic virus infection; Exhaustion; Gene Expression Regulation; Humans; Immune response; Immunity; Inflammation; Innate immunity; Interferon; Interferon regulatory factor; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - metabolism; Interferon stimulatory gene; Interferon Type I - metabolism; IRF; ISG; Signal Transduction; T cell; T-Lymphocytes - immunology; Transcriptional Activation; Virus Diseases - genetics; Virus Diseases - immunology; Virus Diseases - therapy; Immune response; Chronic virus infection; T cell; Exhaustion; Interferon stimulatory gene; Innate immunity; Interferon; Adaptive immunity; IRF; ISG; Interferon regulatory factor
• ISSN: 1044-5323; 1096-3618
• DOI: 10.1016/j.smim.2019.05.001

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.