title: The ubiquitin ligase Riplet is essential for RIG-I-dependent innate immune responses to RNA virus infection.
abstract: RNA virus infection is recognized by the RIG-I-like receptors RIG-I and MDA5, which induce antiviral responses including the production of type I interferons (IFNs) and proinflammatory cytokines. RIG-I is regulated by Lys63-linked polyubiquitination, and three E3 ubiquitin ligases, RNF125, TRIM25, and Riplet, are reported to target RIG-I for ubiquitination. To examine the importance of Riplet in vivo, we generated Riplet-deficient mice. Fibroblasts, macrophages, and conventional dendritic cells from Riplet-deficient animals were defective for the production of IFN and other cytokines in response to infection with several RNA viruses. However, Riplet was dispensable for the production of IFN in response to B-DNA and DNA virus infection. Riplet deficiency abolished RIG-I activation during RNA virus infection, and the mutant mice were more susceptible to vesicular stomatitis virus infection than wild-type mice. These data indicate that Riplet is essential for regulating RIG-I-mediated innate immune response against RNA virus infection in vivo.
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku Sapporo 060-8638, Japan. oshiumi@med.hokudai.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oshiumi
authors.forename: Moeko
authors.initials: M
authors.lastname: Miyashita
authors.forename: Naokazu
authors.initials: N
authors.lastname: Inoue
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000502:physiology; D002478:Cells, Cultured; D004267:DNA Viruses / Q000276:immunology / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D012327:RNA Virus Infections / Q000276:immunology*; D012328:RNA Viruses / Q000276:immunology / Q000502:physiology*; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*; D000097905:Roundabout Proteins
chemical_list: D053468:CARD Signaling Adaptor Proteins; D007370:Interferon Type I; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D044767:Ubiquitin-Protein Ligases; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C557200:Rnf135 protein, mouse