Abstract
West Nile virus (WNV) exists in nature as a genetically diverse population of competing genomes. This high genetic diversity and concomitant adaptive plasticity has facilitated the rapid adaptation of WNV to North American transmission cycles and contributed to its explosive spread throughout the New World. WNV is maintained in nature in a transmission cycle between mosquitoes and birds, with intrahost genetic diversity highest in mosquitoes. The mechanistic basis for this increase in genetic diversity in mosquitoes is poorly understood. To determine whether the high mutational diversity of WNV in mosquitoes is driven by RNA interference (RNAi), we characterized the RNAi response to WNV in the midguts of orally exposed Culex pipiens quinquefasciatus using high-throughput, massively parallel sequencing and estimated viral genetic diversity. Our data demonstrate that WNV infection in orally exposed vector mosquitoes induces the RNAi pathway and that regions of the WNV genome that are more intensely targeted by RNAi are more likely to contain point mutations compared to weakly targeted regions. These results suggest that, under natural conditions, positive selection of WNV within mosquitoes is stronger in regions highly targeted by the host RNAi response. Further, they provide a mechanistic basis for the relative importance of mosquitoes in driving WNV diversification.
Highlights
RNA viruses possess an extraordinary capacity to adapt to changing environments due to their high mutation rate [1]
We demonstrate that West Nile virus (WNV) is targeted by RNA interference, a highly sequence-specific pathway in the mosquito
These results provide a mechanistic explanation for the increasead complexity of WNV populations in mosquitoes: the RNA interference (RNAi) response creates an intracellular environment where rare genotypes are favored
Summary
RNA viruses possess an extraordinary capacity to adapt to changing environments due to their high mutation rate [1]. Recent epidemics of West Nile virus (WNV, Flaviviridae, Flavivirus) and chikungunya virus (CHIKV, Togaviridae, Alphavirus) were driven by relatively small genetic changes that increased the efficiency with which the viruses were transmitted by mosquito vectors (Culex spp. and Aedes albopictus, respectively) [2,3,4]. The change in transmission efficiency has led to the complete displacement of the parental WNV genotype by the derived strain, demonstrating the power of small genetic changes to profoundly influence arbovirus transmission patterns and the importance of mosquitoes in shaping their populations [5]. The underlying mechanism for the increased genetic diversity in mosquitoes, is poorly understood
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