RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA): a new antiviral pathway.
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.
Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, 3000 Arlington Avenue, Mailstop 1021, Toledo, OH, 43614, USA. saurabh.chattopadhyay@utoledo.edu.
Saurabh
S
Chattopadhyay
Cleveland Clinic, Department of Immunology, 9500 Euclid Avenue, NE20, Cleveland, OH, 44195, USA. seng@ccf.org.
Ganes C
GC
Sen
D000818:Animals; D017209:Apoptosis; D000071457:DEAD Box Protein 58 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D011971:Receptors, Immunologic; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58
IRF3; RIPA; innate immunity