Thursday, November 21, 2024
11/21/2024
Arthropod-borne viruses (arboviruses) adapt to local conditions, maximizing their potential to perpetuate and emerge as health threats. The adaptive potential of arboviruses is driven by error-prone replication, which creates a genetically diverse pool of competing virus genotypes within each host. One of the most important ways that the environment is changing is that temperatures are rising. This proposal examines some of the ways that temperature may impact arbovirus evolutionary biology. Aim 1 will address how a comprehensive temperature gradient that includes both constant and fluctuating temperatures with varying means and amplitudes alters natural selection on WNV populations within mosquitoes and the strength of bottlenecks. Our predictions are that fluctuating temperatures will increase the strength of purifying selection, that diversity will be maximized at optimal constant temperatures, and that bottlenecks will become wider as temperature increases. Flaviviruses infections are most frequently initiated by aggregates of virus particles. Aim 2 will address the extent that this occurs in a host- and temperature- dependent manner, bringing our previous work into a more ecologically relevant, realistic context. In the second phase of Aim 2, we will ask whether these genome aggregates can help to facilitate the maintenance of genetic diversity in the WNV population. This is important because population bottlenecks can significantly impact virus fitness, and aggregation of genomes in individual infections may help viruses escape from them. We have found that birds that generate high WNV viremia and are highly infectious to mosquitoes (crows) have significantly more unique WNV genomes per cell than those that have lower viremias (robins). Aim 3 will assess whether this also may occur in mosquitoes. We also will assess the degree to which this phenomenon may allow for the maintenance of low fitness viral genotypes while preventing those of high fitness from gaining dominance. Preliminary data supporting the feasibility of these studies is provided in the application. The significance of this work is that it will provide novel, comprehensive data on the ways that changing environmental conditions such as those that we are now experiencing may alter the fundamental population biology of arboviruses. Arboviruses are uniquely susceptible to these conditions because they must replicate in mosquitoes. This is inherently significant. Our work is also significant because it will provide mechanistic data on how viruses may maintain genetic diversity in the face of both selective and stochastic reductions in genetic diversity. Finally, the significance of our work is that we have provided technical and analytical tools that are broadly useful and have permitted us to collaborate effectively with a wide array of investigators. The proposed studies are technically and conceptually innovative because of the ways that we can combine realistic transmission systems in the lab with barcoded viruses, single cell approaches, and other new molecular tools.
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