CAREER: Deconstructing the Fitness Tradeoffs that Limit Viral Host Range

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。这个研究项目将探索病毒如何适应多种宿主物种。病毒具有适应新环境的非凡能力，但它们感染新宿主的潜力不一定是无限的。在很大程度上，人们认为适应新宿主会降低病原体在其他宿主中的表现或适应性，从而限制了特定病原体可以感染的宿主范围。因此，了解这些权衡如何可以为如何最好地控制和管理病毒性病原体提供重要见解。该研究项目将开发新的计算方法来估计不同环境和尺度下的病原体适应度。这些方法将用于研究番茄斑点枯萎病毒（TSWV）的病毒适应度权衡。TSWV是几种重要作物的主要病原体，其广泛的植物寄主使其成为世界范围内的主要农业威胁。此外，该项目将涉及本科生和研究生的研究，并开发一个虚拟环境，学生可以在其中互动和应对一系列模拟的流行病威胁场景。因此，研究TSWV如何适应新的宿主将有助于深入了解具有广泛宿主范围的多能病毒如何进化，宿主之间的适应性权衡如何限制对多个宿主的同时适应，以及选择是否可以随着时间的推移解决这些适应性权衡，从而导致宿主范围的进一步扩大。通过这个项目，研究人员将开发新的系统动力学出生-死亡模型来研究适应性进化。这些方法将用于估计病原体在不同环境中的传播适应度，甚至可以揭示特定突变如何影响适应度。在开发这些方法的同时，研究人员将对多个宿主的TSWV基因组多样性进行广泛的实地调查，以确定单个病毒基因型在一组作物和本地植物宿主上的适应性。通过将新开发的系统动力学方法与不同宿主上病毒适应度的经验测量相结合，研究人员将能够探索适应度权衡如何塑造通才病毒病原体的宿主范围，以及这些适应度权衡如何随着时间的推移而演变。病毒分离株也将在实验室中进一步在交替宿主之间进行实验传代，以探索选择如何破坏或解决交替宿主之间的适应性权衡。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).This research project will explore how viruses adapt to multiple host species. Viruses have a remarkable capacity to adapt to novel environments, but their potential to infect new hosts is not necessarily limitless. Adapting to a novel host is largely thought to decrease pathogen performance or fitness in other hosts, limiting the range of hosts a given pathogen can infect. Understanding how these tradeoffs could therefore provide major insights into how best to control and manage viral pathogens. This research project will develop new computational methods to estimate pathogen fitness across different environments and scales. These methods will be applied to study viral fitness tradeoffs in tomato spotted wilt virus (TSWV). TSWV is a major pathogen of several important crops and its wide range of plant hosts has allowed it to become a major agricultural threat worldwide. In addition, the project will involve undergraduate and graduate students in the research, and develop a virtual environment in which students can interact and respond to a series of simulated epidemic threat scenarios.Studying how TSWV adapts to novel hosts will therefore provide insight into how a generalist virus with an already broad host range evolves, how fitness tradeoffs between hosts limit simultaneous adaptation to multiple hosts, and whether selection can resolve these fitness tradeoffs over time, leading to further host range expansion. Through this project, the researchers will develop new phylodynamic birth-death models for studying adaptive evolution. These methods will be used to estimate the transmission fitness of pathogens in different environments and can even reveal how particular mutations influence fitness. Along with developing these methods, the researchers will conduct an extensive field survey of TSWV genomic diversity across multiple hosts to determine the fitness of individual viral genotypes on a panel of crops and native plant hosts. By combining the newly developed phylodynamic methods with empirical measures of viral fitness on different hosts, the researchers will then be able to explore how fitness tradeoffs shape the host range of a generalist viral pathogen and how these fitness tradeoffs evolve over time. Viral isolates will also be further experimentally passaged between alternate hosts in the lab to explore how selection can breakdown or resolve fitness tradeoffs between alternate hosts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.