Dengue virus capsid protein interaction with nucleic acids

Dengue virus (DENV) transmission has greatly increased in the last decade, in part due to the geographical expansion of its vector, the Aedes spp. mosquitoes. These arthropods are now found even in temperate climates, including Europe, where outbreaks have already occurred. A better understanding of the virus life cycle is essential, as it may enable the development of specific treatments or therapies which are currently lacking. However, recent breakthroughs concerning the biologically relevant viral capsid (C) protein structure and function are encouraging. It is now clear the C protein binds both to host lipid droplets and to the viral genome, a set of interactions that is crucial for viral encapsidation and replication. Previously, we studied DENV C protein interaction with lipid droplets, at the molecular level. Here, we examine how the association of DENV C protein with the viral genome occurs. Using DENV C protein and single-stranded DNA (ssDNA) sequences analogous to previously identified important regions of the viral genome, we biophysically characterize their interactions. A decrease in fluorescence intensity and lifetime, an increase in both anisotropy and hydrodynamic diameter, as well as changes in the protein’s secondary structure, were observed upon binding to ssDNA. These changes are consistent with molecular condensation and raise the possibility of liquid-liquid phase separation involvement in DENV C-nucleic acid complex formation. These findings may be useful for the development of future therapeutic strategies based on nucleic acids, not only for DENV but also for other related viruses.