CAREER: Deconstructing the Fitness Tradeoffs that Limit Viral Host Range

North Carolina State University, Raleigh NC

Investigators

Abstract

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.