How do flaviviruses orchestrate viral RNA replication and virion assembly?

Flaviviruses, including Zika virus and Dengue virus, are mosquito-borne pathogens of public health concern, with more than 2.2 billion people at risk of infection. While many cases remain asymptomatic, symptomatic infections lead to rash, fever, arthralgia, myalgia, headache, retro-orbital pain, and conjunctivitis. More serious complications include hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, congenital abnormalities, and fetal death. Despite decades of research, our understanding of the fundamental biology of flaviviruses, including how they replicate their genomes and build viral particles, remains rudimentary. Today, the technologies exist to allow us to tease apart the roles of the main viral proteins in mediating these processes. Herein, we are studying two viral proteins known to participate in both the process of viral genome replication and viral particle assembly, and are therefore highly lucrative targets for antiviral intervention. Insight into these processes, and how the viral proteins interact with one another and with the viral genome, will allow us to develop novel antiviral strategies and design new vaccination approaches for these important human pathogens. Moreover, given the conservation of these viral proteins across the flavivirus genus, our results are likely to be applicable to several other important human pathogens.