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Title: Discovery of Dengue Virus Host Factors
Keywords: flavivirus, dengue virus, interferon, translation, non-coding RNA, immune antagonist
Issue Date: 20-Feb-2014
Citation: KATELL BIDET (2014-02-20). Discovery of Dengue Virus Host Factors. ScholarBank@NUS Repository.
Abstract: Viral RNA-host protein interactions are critical for replication of flaviviruses, a genus of positive-strand RNA viruses comprising major vector-borne human pathogens including dengue viruses (DENV). We examined three conserved host RNA-binding proteins (RBPs) G3BP1, G3BP2 and CAPRIN1 in dengue virus (DENV-2) infection and found all to be novel regulators of the interferon (IFN) response against DENV-2. The three RBPs were required for translation of interferon stimulated gene (ISG) mRNAs, which identifies them as novel regulators of the antiviral state. This antiviral activity was antagonized by the abundant DENV-2 non-coding subgenomic flaviviral RNA (sfRNA), which bound to G3BP1, G3BP2 and CAPRIN1, inhibited their activity and lead to profound inhibition of ISG mRNA translation. This work describes a new and unexpected level of regulation for interferon stimulated gene expression and presents the first mechanism of action for an sfRNA as a molecular sponge of anti-viral effectors.
Appears in Collections:Ph.D Theses (Open)

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