[Innate immune response to RNA virus infection].
Viral RNA is recognized by RIG-I-like receptors and Toll-like receptors. RIG-I is a cytoplasmic viral RNA sensor. High Mobility Group Box (HMGB) proteins and DExD/H box RNA helicases, such as DDX3 and 60, associate with viral RNA. Those proteins promotes the RIG-I binding to viral RNA. RIG-I triggers the signal via IPS-1 adaptor molecule to induce type I IFN. RIG-I harbors Lys63-linked polyubiquitination by Riplet and TRIM25 ubiquitin ligases. The polyubiquitination is essential for RIG-I-mediated signaling. Toll-like receptors are located in endosome. TLR3 recognizes viral double-stranded RNA, and TLR7 and 8 recognize single-strand RNA. Virus has the ability to suppress these innate immune response. For example, to inhibit RIG-I-mediated signaling, HCV core protein suppresses the function of DDX3. In addition, HCV NS3-4A protein cleaves IPS-1 to inhibit the signal. Molecular mechanism of how viral RNA is recognized by innate immune system will make great progress on our understanding of how virus escapes from host immune system.
Graduate School of Medicine, Hokkaido University. oshiumi@med.hokudai.ac.jp
Hiroyuki
H
Oshiumi
Misako
M
Matsumoto
Tsukasa
T
Seya
D016207:Cytokines / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism / Q000502:physiology; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D012327:RNA Virus Infections / Q000276:immunology*; D012367:RNA, Viral / Q000276:immunology; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors / Q000502:physiology; D025801:Ubiquitin / Q000502:physiology
D016207:Cytokines; D012367:RNA, Viral; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D025801:Ubiquitin; C119332:DDX3X protein, human; C452820:RIGI protein, human; C561888:DDX60 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases