title: Retinoic acid-inducible gene I-inducible miR-23b inhibits infections by minor group rhinoviruses through down-regulation of the very low density lipoprotein receptor.
abstract: In mammals, viral infections are detected by innate immune receptors, including Toll-like receptor and retinoic acid inducible gene I (RIG-I)-like receptor (RLR), which activate the type I interferon (IFN) system. IFN essentially activates genes encoding antiviral proteins that inhibit various steps of viral replication as well as facilitate the subsequent activation of acquired immune responses. In this study, we investigated the expression of non-coding RNA upon viral infection or RLR activation. Using a microarray, we identified several microRNAs (miRNA) specifically induced to express by RLR signaling. As suggested by Bioinformatics (miRBase Target Data base), one of the RLR-inducible miRNAs, miR-23b, actually knocked down the expression of very low density lipoprotein receptor (VLDLR) and LDLR-related protein 5 (LRP5). Transfection of miR-23b specifically inhibited infection of rhinovirus 1B (RV1B), which utilizes the low density lipoprotein receptor (LDLR) family for viral entry. Conversely, introduction of anti-miRNA-23b enhanced the viral yield. Knockdown experiments using small interfering RNA (siRNA) revealed that VLDLR, but not LRP5, is critical for an efficient infection by RV1B. Furthermore, experiments with the transfection of infectious viral RNA revealed that miR-23b did not affect post-entry viral replication. Our results strongly suggest that RIG-I signaling results in the inhibitions of infections of RV1B through the miR-23b-mediated down-regulation of its receptor VLDLR.
authors.affiliation: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Ouda
authors.forename: Koji
authors.initials: K
authors.lastname: Onomoto
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Takahasi
authors.forename: Michael R
authors.initials: MR
authors.lastname: Edwards
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kato
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yoneyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
mesh_terms: D001483:Base Sequence; D019295:Computational Biology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012367:RNA, Viral / Q000378:metabolism; D011971:Receptors, Immunologic; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics*; D012229:Rhinovirus / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation; D014779:Virus Replication / Q000235:genetics
chemical_list: C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral; D011971:Receptors, Immunologic; D011973:Receptors, LDL; C036053:VLDL receptor; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases