title: RNA species generated in vaccinia virus infected cells activate cell type-specific MDA5 or RIG-I dependent interferon gene transcription and PKR dependent apoptosis.
abstract: RNA species produced during virus replication are pathogen-associated molecular patterns (PAMPs) triggering cellular innate immune responses including induction of type I interferon expression and apoptosis. Pattern recognition receptors (PRRs) for these RNAs include the retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) RIG-I and melanoma differentiation associated gene 5 (MDA5) and the dsRNA dependent protein kinase (PKR). Currently, poxvirus PAMPs and their associated PRRs are not well characterized. We report that RNA species generated in vaccinia infected cells can activate MDA5 or RIG-I dependent interferon-β (IFN-β) gene transcription in a cell type-specific manner. These RNA species also induce the activation of apoptosis in a PKR dependent, but MDA5 and RIG-I independent, manner. Collectively our results demonstrate that RNA species generated during vaccinia virus replication are major PAMPs activating apoptosis and IFN-β gene transcription. Moreover, our results delineate the signaling pathways involved in the recognition of RNA-based poxvirus PAMPs.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada R3T 2N2.
authors.forename: Chad
authors.initials: C
authors.lastname: Myskiw
authors.forename: Janilyn
authors.initials: J
authors.lastname: Arsenio
authors.forename: Evan P
authors.initials: EP
authors.lastname: Booy
authors.forename: Craig
authors.initials: C
authors.lastname: Hammett
authors.forename: Yvon
authors.initials: Y
authors.lastname: Deschambault
authors.forename: Spencer B
authors.initials: SB
authors.lastname: Gibson
authors.forename: Jingxin
authors.initials: J
authors.lastname: Cao
mesh_terms: D017209:Apoptosis / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics*; D011971:Receptors, Immunologic; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D012367:RNA, Viral; D011971:Receptors, Immunologic; D016899:Interferon-beta; D011494:Protein Kinases; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1