Specific Interaction of DDX6 with an RNA Hairpin in the 3′ UTR of the Dengue Virus Genome Mediates G <sub>1</sub> Phase Arrest
Opas Choksupmanee, Worapol Tangkijthavorn, Kenneth Hodge, Krittanai Trisakulwattana, Worawich Phornsiricharoenphant, Veerakorn Narkthong, Sarun Tulakarnwong, Chumpol Ngamphiw, Sissades Tongsima, Sarin Chimnaronk
Abstract
Dengue virus (DENV) is transmitted by mosquitoes to humans, infecting 390 million individuals per year globally. About 20% of infected patients shows a spectrum of clinical manifestation, ranging from a mild flu-like syndrome, to dengue fever, to life-threatening severe dengue diseases, including dengue hemorrhagic fever and dengue shock syndrome. There is currently no specific treatment for dengue diseases, and the molecular mechanism underlying dengue pathogenesis remains poorly understood. In this study, we combined biochemical, bioinformatics, high-content analysis and RNA sequencing approaches to characterize a highly conserved interface of the RNA genome of DENV with a human factor named DDX6 in infected cells. The significance of our research is in identifying the mechanism for a viral strategy to alter host cell fates, which conceivably allows us to generate a model for live-attenuated vaccine and the design of new therapeutic reagent for dengue diseases.