Cell type-specific involvement of RIG-I in antiviral response.
Toll-like receptors (TLRs) play an important role in antiviral response by recognizing viral components. Recently, a RNA helicase, RIG-I, was also suggested to recognize viral double-stranded RNA. However, how these molecules contribute to viral recognition in vivo is poorly understood. We show by gene targeting that RIG-I is essential for induction of type I interferons (IFNs) after infection with RNA viruses in fibroblasts and conventional dendritic cells (DCs). RIG-I induces type I IFNs by activating IRF3 via IkappaB kinase-related kinases. In contrast, plasmacytoid DCs, which produce large amounts of IFN-alpha, use the TLR system rather than RIG-I for viral detection. Taken together, RIG-I and the TLR system exert antiviral responses in a cell type-specific manner.
Kato
Hiroki
H
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Sato
Shintaro
S
Yoneyama
Mitsutoshi
M
Yamamoto
Masahiro
M
Uematsu
Satoshi
S
Matsui
Kosuke
K
Tsujimura
Tohru
T
Takeda
Kiyoshi
K
Fujita
Takashi
T
Takeuchi
Osamu
O
Akira
Shizuo
S
D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018390:Gene Targeting; D051550:I-kappa B Kinase; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009521:Newcastle Disease / Q000201:enzymology / Q000276:immunology; D009522:Newcastle disease virus / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020365:RNA Helicases / Q000235:genetics / Q000502:physiology*; D012327:RNA Virus Infections / Q000201:enzymology* / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D051193:Toll-Like Receptors; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases