title: Induction of type I interferon by adenovirus-encoded small RNAs.
abstract: Transduction with replication-incompetent recombinant adenovirus (Ad) vectors results in a rapid activation of innate immune responses, such as inflammatory cytokine production and subsequent tissue damage. The precise mechanisms of the innate immune responses induced by Ad vectors remain to be clarified. Possible components of Ad vectors that activate innate immune responses are the capsid protein, the viral genome (DNA), and viral transcripts. In the present study, we demonstrate that virus-associated RNAs (VA-RNAs), which are small RNAs transcribed by RNA polymerase III, induce the production of type I IFN (IFN-α and IFN-β), but they do not induce the production of inflammatory cytokines (IL-6 and IL-12), in mouse embryonic fibroblasts (MEFs) and granulocyte-macrophage colony-stimulating factor-generated bone marrow-derived dendritic cells (GM-DCs). We also show that IFN-β promoter stimulator-1 is involved in VA-RNA-dependent IFN-β production in MEFs and is partially involved in type I IFN production in GM-DCs. This study provides important insight into the mechanisms of Ad vector-triggered innate immune responses, which may lead to more advanced and rational Ad vector designs for gene therapies and vaccine applications.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabata
authors.forename: Emi
authors.initials: E
authors.lastname: Kouyama
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Katayama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Kurachi
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012313:RNA / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D007370:Interferon Type I; D012313:RNA; C512612:MAVS protein, mouse