Dengue Virus Capsid Protein Interaction With Nucleic Acids

ABSTRACT Dengue virus (DENV) transmission has greatly increased in the last decade, partly due to the geographical expansion of Aedes spp. mosquitoes. These arthropods are now found even in temperate climates, including Europe, where outbreaks have occurred. A better understanding of the life cycle is essential, as it may enable the development of specific treatments or therapies, which are currently lacking. Recent breakthroughs concerning the viral capsid (C) protein structure and function are encouraging. It is now clear that the C protein binds both to host lipid droplets and to the viral genome—interactions crucial for viral encapsidation and replication. Here, we investigate how DENV C associates with the viral genome. Using DENV C and single‐stranded DNA sequences analogous to relevant genomic regions, we biophysically characterize their interaction. A decrease in fluorescence intensity and lifetime, as well as changes in the protein secondary structure, were observed upon interacting with single‐stranded DNA. These results are consistent with molecular condensation, supporting a possible liquid–liquid phase separation contributing to DENV C–nucleic acid complex formation.