The Role of the Flavivirus Replicase in Viral Diversity and Adaptation

Flaviviruses include several emerging and re-emerging arboviruses which cause millions of infections each year. Although relatively well-studied, much remains unknown regarding the mechanisms and means by which these viruses readily alternate and adapt to different hosts and environments. Here, we review a subset of the different aspects of flaviviral biology which impact host switching and viral fitness. These include the mechanism of replication and structural biology of the NS3 and NS5 proteins, which reproduce the viral genome; rates of mutation resulting from this replication and the role of mutational frequency in viral fitness; and the theory of quasispecies evolution and how it contributes to our understanding of genetic and phenotypic plasticity.