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Dengue Virus NS5 Transcribes Metabolite-Capped, RIG-I Sensitive vRNAs

Abstract : Eukaryotic nuclear and mitochondrial RNA polymerases (RNAPs) can cap RNAs by initiating with the non-canonical initiating nucleotide (NCIN) nicotinamide adenine dinucleotide (both NAD+ and NADH). Similarly, recently Dengue viral RNAs (vRNA) have been observed with NCIN caps, but how these vRNAs are capped is unknown. Here we show directly that Dengue virus's (DENV) RNAP NS5 can utilize both NAD+ and NADH, as well as flavin adenine dinucleotide and dephospho-coenzyme A, as initiating nucleotides during RNA transcription in place of DENV's well-conserved initiating adenine. In addition, we demonstrate that NCIN-capped dsRNAs can bind to the innate immune receptor RIG-I with KD's between 3 and 6 nM. RIG-I can also use these NCIN-capped dsRNAs to initiate robust interferon production. Taken with the previously published results that NAD+-capped mRNAs cannot be translated, we propose that NCIN-capped DENV vRNA represents a newly discovered mechanism of metabolite-mediated immunity that generates translation-deficient, highly immunogenic vRNAs.
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https://hal-amu.archives-ouvertes.fr/hal-03426114
Contributor : Julien Caugant Connect in order to contact the contributor
Submitted on : Friday, November 12, 2021 - 8:47:57 AM
Last modification on : Wednesday, January 19, 2022 - 4:58:35 PM

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Brandon Schweibenz, Mihai Solotchi, Etienne Decroly, Barbara Selisko, Bruno Canard, et al.. Dengue Virus NS5 Transcribes Metabolite-Capped, RIG-I Sensitive vRNAs. Biophysical Journal, Biophysical Society, 2021, 120 (3), pp.135a. ⟨10.1016/j.bpj.2020.11.1017⟩. ⟨hal-03426114⟩

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