Arbovirus population biology: temperature impacts on selection and collective dynamics

虫媒病毒种群生物学：温度对选择和集体动态的影响

• 批准号: 10568405
• 负责人: Gregory David Ebel
• 金额: $ 34.84万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10568405
• 关键词: 2019-nCoV; Address; Alphavirus; Antibodies; Arboviruses; Bar Codes; Biology; Biometry; Birds; Cells; Chikungunya virus; Collaborations; Competence; Crows; Culex (Genus); Culicidae; Data; Disease; Disease Outbreaks; Ecology; Environment; Evolution; Face; Feasibility Studies; Flaviviridae; Flavivirus; Flavivirus Infections; Flow Cytometry; Funding; Future; Genetic Variation; Genome; Genotype; Geography; Goals; Health; Human; Humanities; Incubated; Individual; Infection; Insecticide Resistance; Knowledge; Literature; Maintenance; Medicine; Midgut; Molecular; Molecular Biology; Natural Selections; Nature; Nucleotides; Phase; Population; Population Biology; Population Genetics; Population Heterogeneity; Predisposition; Public Health; RNA Sequences; RNA Viruses; Research; Research Personnel; Robin bird; Role; Salivary Glands; Shapes; System; Temperature; Testing; Time; Togaviridae; Urbanization; Vaccines; Variant; Vertebrates; Viremia; Virion; Virus; West Nile virus; Work; Zika Virus; analytical tool; environmental change; experience; fitness; innovation; land use; multidisciplinary; mutant; novel; prevent; theories; tool; transmission process; vector; vector competence; vector mosquito; viral fitness; virology; virus genetics

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.

节肢动物传播的病毒（虫媒病毒）适应当地条件，最大限度地发挥其永久存在和传播的潜力 成为健康威胁。虫媒病毒的适应潜力是由容易出错的复制驱动的，这 在每个宿主内创建一个具有遗传多样性的竞争性病毒基因型库。最重要的之一 环境发生变化的方式是温度升高。该提案审查了一些 温度可能影响虫媒病毒进化生物学的方式。 目标 1 将解决包括恒定和波动的综合温度梯度如何 不同平均值和幅度的温度改变了西尼罗河病毒种群的自然选择 蚊子和强度的瓶颈。我们的预测是，温度波动会增加 纯化选择的强度，多样性将在最佳恒定温度下最大化，并且 随着温度升高，瓶颈将变得更宽。黄病毒感染最常由 病毒颗粒的聚集体。目标 2 将解决这种情况在宿主和温度中发生的程度 依赖的方式，将我们之前的工作带入一个更与生态相关、更现实的背景中。在 Aim 2的第二阶段，我们会问这些基因组聚合体是否可以帮助促进维护 西尼罗河病毒种群的遗传多样性。这很重要，因为人口瓶颈会显着 影响病毒的适应性，个体感染中基因组的聚集可能有助于病毒逃离它们。 我们发现产生高西尼罗河病毒血症且对蚊子（乌鸦）具有高度传染性的鸟类 与病毒血症较低的知更鸟（知更鸟）相比，每个细胞的独特 WNV 基因组明显更多。目标3将 评估这种情况是否也可能发生在蚊子身上。我们还将评估这种现象的程度 可能允许维持低适应度病毒基因型，同时防止高适应度病毒基因型获得 统治地位。申请中提供了支持这些研究可行性的初步数据。 这项工作的意义在于，它将提供关于改变方式的新颖、全面的数据。 我们现在所经历的环境条件可能会改变基本人口 虫媒病毒生物学。虫媒病毒对这些条件特别敏感，因为它们必须在 蚊子。这本身就具有重大意义。我们的工作也很重要，因为它将提供机械数据 关于病毒如何在遗传选择性和随机减少的情况下保持遗传多样性 多样性。最后，我们工作的意义在于我们提供了技术和分析工具 广泛有用，使我们能够与广泛的研究人员有效合作。拟议的 研究在技术和概念上都是创新的，因为我们可以将现实结合起来 使用条形码病毒、单细胞方法和其他新分子工具在实验室中进行传输系统。