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Abstract
<p class="first" id="d1513135e142">The flavivirus genus comprises major human pathogens,
such as Dengue (DENV) and Zika
(ZIKV) viruses. RIG-I and MDA5 are key cytoplasmic pathogen recognition receptors
that are implicated in detecting viral RNAs. Here, we show that RNAs that co-purified
with RIG-I during DENV infection are immuno-stimulatory, whereas RNAs bound to MDA5
are not. An affinity purification method combined with next-generation sequencing
(NGS) revealed that the 5' region of the DENV genome is recognized by RIG-I. No DENV
RNA was bound to MDA5. In vitro production of fragments of the DENV genome confirmed
the NGS data and revealed that the 5' end of the genome, when bearing 5'-triphosphates,
is the RIG-I ligand. The 5' region of the ZIKV genome is also a RIG-I agonist. We
propose that RIG-I binds to the highly structured and conserved 5' region of flavivirus
nascent transcripts before capping and that this mechanism leads to interferon secretion
by infected cells.
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