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• W2034656056 endingPage "620" @default.
• W2034656056 startingPage "606" @default.
• W2034656056 abstract "ABSTRACT Chikungunya virus (CHIKV) is an arthritogenic mosquito-transmitted alphavirus that is undergoing reemergence in areas around the Indian Ocean. Despite the current and potential danger posed by this virus, we know surprisingly little about the induction and evasion of CHIKV-associated antiviral immune responses. With this in mind we investigated innate immune reactions to CHIKV in human fibroblasts, a demonstrable in vivo target of virus replication and spread. We show that CHIKV infection leads to activation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent transcription of IRF3-dependent antiviral genes, including beta interferon (IFN-β). IRF3 activation occurs by way of a virus-induced innate immune signaling pathway that includes the adaptor molecule interferon promoter stimulator 1 (IPS-1). Despite strong transcriptional upregulation of these genes, however, translation of the corresponding proteins is not observed. We further demonstrate that translation of cellular (but not viral) genes is blocked during infection and that although CHIKV is found to trigger inactivation of the translational molecule eukaryotic initiation factor subunit 2α by way of the double-stranded RNA sensor protein kinase R, this response is not required for the block to protein synthesis. Furthermore, overall diminution of cellular RNA synthesis is also observed in the presence of CHIKV and transcription of IRF3-dependent antiviral genes appears specifically blocked late in infection. We hypothesize that the observed absence of IFN-β and antiviral proteins during infection results from an evasion mechanism exhibited by CHIKV that is dependent on widespread shutoff of cellular protein synthesis and a targeted block to late synthesis of antiviral mRNA transcripts." @default.
• W2034656056 created "2016-06-24" @default.
• W2034656056 creator A5012696027 @default.
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• W2034656056 date "2011-01-01" @default.
• W2034656056 modified "2023-09-25" @default.
• W2034656056 title "Chikungunya Virus Induces IPS-1-Dependent Innate Immune Activation and Protein Kinase R-Independent Translational Shutoff" @default.
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• W2034656056 doi "https://doi.org/10.1128/jvi.00767-10" @default.
• W2034656056 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3014158" @default.
• W2034656056 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20962078" @default.

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