Regulation of interferon regulatory factor 3-dependent innate immunity by the HCV NS3/4A protease.
Interferon regulatory factor 3 (IRF-3) is a ubiquitously expressed latent cellular transcription factor that plays a pivotal role in control of innate, type I interferon (IFN) antiviral responses. After viral infections, IRF-3 is activated by specific C-terminal phosphorylation, which induces its dimerization and nuclear translocation, whereupon IRF-3 activates the transcription of type I IFNs and a number of other antiviral effector genes. Many viruses have evolved strategies that antagonize signaling mechanisms leading to IRF-3 activation. Recent studies have shown that hepatitis C virus blocks IRF-3 activation and subsequent IFN induction by cleaving critical cellular substrates within the intracellular antiviral signaling pathways upstream of IRF-3 with its major protease, NS3/4A.
Li
Kui
K
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D016174:Hepacivirus / Q000201:enzymology* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D018613:Microscopy, Confocal; D008967:Molecular Biology / Q000379:methods*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D012330:RNA, Double-Stranded / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D010253:Respirovirus Infections / Q000276:immunology; D029082:Sendai virus / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D050838:Interferon Regulatory Factor-3; D008156:Luciferases; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D001616:beta-Galactosidase; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases