Structure of the Dengue Virus RNA Promoter

Abstract

Dengue virus, a single-stranded positive sense RNA virus, is the most prevalent mosquito-borne pathogen in the world. Like all RNA viruses, it uses conserved structural elements within its genome to control essential replicative steps. A 70 nucleotides stem-loop RNA structure (called SLA) found at the 5-end of the genome of all flaviviruses, functions as the promoter for viral replication. This highly conserved structure interacts with the viral polymerase NS5 to initiate RNA synthesis. Here we report the NMR structure of a monomeric SLA from Dengue virus serotype 1, assembled to high-resolution from independently folded structural elements. The DENV1 SLA has an L-shape structure, where the top and side helices are coaxially-stacked and the bottom helix is roughly perpendicular to them. Because the sequence is highly conserved among different flavivirus genomes, it is likely that the three-dimensional fold and local structure of SLA are also conserved among flaviviruses and required for efficient replication. This work provides structural insight into the Dengue promoter and provides the foundation for the discovery of new antiviral drugs that target this essential replicative step.