RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA): a new antiviral pathway

• Published in: Protein & Cell Vol. 8; no. 3; pp. 165 - 168
• Main Authors: Chattopadhyay, Saurabh, Sen, Ganes C.
• Format: Journal Article Book Review
• Language: English
• Published: Beijing Higher Education Press 01.03.2017; Springer Nature B.V; Oxford University Press
• Subjects: Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell Biology; DEAD Box Protein 58 - genetics; DEAD Box Protein 58 - immunology; DEAD Box Protein 58 - metabolism; Developmental Biology; Human Genetics; Humans; Immunity, Innate; innate immunity; Interferon Regulatory Factor-3 - genetics; Interferon Regulatory Factor-3 - immunology; Interferon Regulatory Factor-3 - metabolism; IRF3; Life Sciences; Mice; Mini-Review; Protein Science; Receptors, Immunologic; RIPA; Stem Cells; Virus Diseases - genetics; Virus Diseases - immunology; Virus Diseases - metabolism; IRF3; innate immunity; RIPA
• ISSN: 1674-800X; 1674-8018
• DOI: 10.1007/s13238-016-0334-x

The innate immune response is the first line of host defense to eliminate viral infection. Pattern recognition receptors in the cytosol, such as RIG-I-like receptors (RLR) and Nod-like receptors (NLR), and membrane bound Toll like receptors (TLR) detect viral infection and initiate transcription of a cohort of antiviral genes, including interferon (IFN) and interferon stimulated genes (ISGs), which ultimately block viral replication. Another mechanism to reduce viral spread is through RIPA, the RLR-induced IRF3-mediated pathway of apoptosis, which causes infected cells to undergo premature death. The transcription factor IRF3 can mediate cellular antiviral responses by both inducing antiviral genes and triggering apoptosis through the activation of RIPA. The mechanism of IRF3 activation in RIPA is distinct from that of transcriptional activation; it requires linear polyubiquitination of specific lysine residues of IRF3. Using RIPA-active, but transcriptionally inactive, IRF3 mutants, it was shown that RIPA can prevent viral replication and pathogenesis in mice.