title: RIG-I mediates nonsegmented negative-sense RNA virus-induced inflammatory immune responses of primary human astrocytes.
abstract: While astrocytes produce key inflammatory mediators following exposure to neurotropic nonsegmented negative-sense RNA viruses such as rabies virus and measles virus, the mechanisms by which resident central nervous system (CNS) cells perceive such viral challenges have not been defined. Recently, several cytosolic DExD/H box RNA helicases including retinoic acid-inducible gene I (RIG-I) have been described that function as intracellular sensors of replicative RNA viruses. Here, we demonstrate that primary human astrocytes constitutively express RIG-I and show that such expression is elevated following exposure to a model neurotropic RNA virus, vesicular stomatitis virus (VSV). Evidence for the functional nature of RIG-I expression in these cells comes from the observation that this molecule associates with its downstream effector molecule, interferon promoter stimulator-1, following VSV infection and from the finding that a specific ligand for RIG-I elicits astrocyte immune responses. Importantly, RIG-I knockdown significantly reduces inflammatory cytokine production by VSV-infected astrocytes and inhibits the production of soluble neurotoxic mediators by these cells. These findings directly implicate RIG-I in the initiation of inflammatory immune responses by human glial cells and provide a potential mechanism underlying the neuronal cell death associated with acute viral CNS infections.
authors.affiliation: Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Furr
authors.forename: Megan
authors.initials: M
authors.lastname: Moerdyk-Schauwecker
authors.forename: Valery Z
authors.initials: VZ
authors.lastname: Grdzelishvili
authors.forename: Ian
authors.initials: I
authors.lastname: Marriott
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology*; D001921:Brain / Q000166:cytology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D003720:Densitometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D015850:Interleukin-6 / Q000378:metabolism; D012328:RNA Viruses / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D011971:Receptors, Immunologic; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015850:Interleukin-6; C505371:MAVS protein, human; C498143:RELA protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases