title: The TAR-RNA binding protein is required for immunoresponses triggered by Cardiovirus infection.
abstract: LGP2 and MDA5 cooperate to detect viral RNA in the cytoplasm of Picornavirus-infected cells and activate innate immune responses. To further define regulatory components of RNA recognition by LGP2/MDA5, a yeast two-hybrid screen was used to identify LGP2-interacting proteins. The screening has identified the TAR-RNA binding protein (TRBP), which is known to be an essential factor for RNA interference (RNAi). Immuno-precipitation experiments demonstrated that TRBP interacted specifically with LGP2 but not with related RIG-I-like receptors, RIG-I or MDA5. siRNA knockdown experiments indicate that TRBP is important for Cardiovirus-triggered interferon responses, but TRBP is not involved in Sendai virus-triggered interferon response that is mediated mainly by RIG-I. To support functional interaction with LGP2, overexpressed TRBP increased Cardiovirus-triggered interferon promoter activity only when LGP2 and MDA5 are co-expressed but not MDA5 alone. Together, our findings illustrate a possible connection between an RNAi-regulatory factor and antiviral RNA recognition that is specifically required for a branch of the virus induced innate immune response.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan. Electronic address: akikomuro@nupals.ac.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Komuro
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Division of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo 164-8530, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Negoro
authors.affiliation: Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL 33136, USA.
authors.forename: Glen N
authors.initials: GN
authors.lastname: Barber
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Curt M
authors.initials: CM
authors.lastname: Horvath
mesh_terms: D000818:Animals; D017943:Cardiovirus / Q000472:pathogenicity; D018188:Cardiovirus Infections / Q000276:immunology / Q000378:metabolism*; D002522:Chlorocebus aethiops; D000071457:DEAD Box Protein 58 / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1 / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D029082:Sendai virus / Q000472:pathogenicity; D014709:Vero Cells; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D000071457:DEAD Box Protein 58; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta; D020365:RNA Helicases; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D000099253:Trans-Activation Responsive RNA-Binding Protein; C520569:DHX58 protein, human; C452820:RIGI protein, human; C452815:IFIH1 protein, human
keywords: LGP2; MDA5; Picornavirus; RIG-I-like receptors; TRBP; Type-I interferon