Quasispecies Dynamics of West Nile Virus in Avian Reservoir Hosts

Arthropod-borne viruses (arboviruses), including West Nile (WNV), dengue, chikungunya and Japanese encephalitis viruses, are some of the most dangerous emerging infectious diseases. The high mutability of these RNA viruses facilitates rapid adaptation and emergence into novel hosts, posing significant challenges to public health, agriculture and wildlife conservation. Within a host, arboviruses exist as quasispecies or a population of related but distinct genetic variants that interact cooperatively on a functional level, and collectively contribute to the characteristics of the population.

The current work builds on a recent study in which WNV was subject to five sequential passages through each of three bird species (American crows, robins and house sparrows). Next-gen sequencing of the resulting populations revealed that WNV populations passaged in crows, the most disease-susceptible of the three species tested, contained the most unique mutations but the lowest average mutation frequency.

Here, we seek to elucidate the distribution of mutations accrued by WNV populations during passage in each of the three host species by conducting mutation hotspot/coldspot analysis for coding and non-coding regions of the WNV genome. Additionally, we test whether RNA secondary structure in the 5’ and 3’ non-coding regions of the genome, which are critical for WNV replication, influences the distribution of mutational hotspots and coldspots, and how, in turn, mutations in these regions influence secondary structure.

Understanding how the interplay between mutation and RNA structure influences arbovirus quasispecies diversity will not only extend current understanding of RNA virus evolution but may also lead to better antiviral therapies.