Untersuchungen zur Suppression der durch doppelsträngige RNA induzierten IFN-beta-Expression durch das Hepatitis A-Virus: Inhibition der RIG-I- und TLR3-vermittelten Signalwegezur Aktivierung des Transkriptionsfaktors IRF-3

Vallbracht, AngelikaFensterl, VolkerVolkerFensterl2020-03-092020-03-092006-02-22https://media.suub.uni-bremen.de/handle/elib/2206The subject of this dissertation is the suppression of interferon-beta induction by hepatitis A virus (HAV), which is mediated by inhibition of activation of transcription factor IRF-3. In a first approach to localize the cellular target of HAV in the two dsRNA-induced signaling pathways leading to the activation of IRF-3, which are mediated by RIG-I and TLR3, respectively, nuclear translocation of IRF-3 was analyzed by using GFP-IRF-3, and poly(IC) transfection or NDV infection as activating stimuli. HAV efficiently suppressed transloaction of IRF-3, so the upstream cytoplasmic signaling pathway components were examined by reporter assays after overexpression, monitoring IFN-beta-enhancer and IRF-3-activation. It is demonstrated that HAV blocks the RIG-I-mediated pathway upstream of the IRF-3 kinases IKKe and TBK1 to block IFN-beta induction, and that HAV negatively affects the TLR3 pathway as well.deinfo:eu-repo/semantics/openAccesshepatitis A virusinterferonIFN-betaIRF-3RIG-ITLR3572Untersuchungen zur Suppression der durch doppelsträngige RNA induzierten IFN-beta-Expression durch das Hepatitis A-Virus: Inhibition der RIG-I- und TLR3-vermittelten Signalwegezur Aktivierung des Transkriptionsfaktors IRF-3Examination of the suppression of double-stranded RNA-induced IFN-beta expression by hepatitis A virus: Inhibition of the RIG-I- and TLR3-mediated signaling pathways leading to the activation of IRF-3Dissertationurn:nbn:de:gbv:46-diss000102621