Virulence Evolution After Viral Host Jump and Emergence

Whether a newly emerged pathogen will become more or less harmful to its host over time is key to predicting the severity of disease outbreaks. When new infectious diseases emerge, the effects on humans, agriculture and wildlife are sometimes devastating, as exemplified by Ebola, avian influenza, and West Nile virus. However, other emergent diseases are much less severe, and may even go unnoticed. The ability to predict the level of harm (i.e. virulence) that an emergent pathogen will cause is limited. This project will improve our ability to predict the severity of emerging diseases by identifying the factors that influence changes in virulence after the infection of a new host species. An extensive body of work has attempted to address this question. Almost all this work has the same shortcoming, key data are not available from the very start of the host-pathogen interaction. Host jumps mark the beginning of a host-pathogen interaction and they therefore provide the only opportunity to study entire trajectories of virulence evolution. The fish virus IHNV (infectious hematopoietic necrosis virus) in rainbow trout and salmon is one of the few systems where samples are available to look at these changes from the beginning for two, independent host jumps, making it an ideal research model. Insights from the study of these host jumps will inform how best to allocate resources to combat the public health, economic, and biodiversity impacts of emerging diseases. The project will also involve building capacity for the management of infectious disease through the education and training of graduate students, undergraduates, and technicians, with a focus on under-represented groups.

Whether the virulence of a pathogen will evolve upwards or downward after emergence in a new host, is a foundational question in evolutionary ecology and infectious disease management. Suitable systems for such studies are rare because they require 1) an extensive collection of pathogen isolates sampled before and after host jumps, which span enough time for evolution to occur, 2) ecologically relevant ancestral and new hosts in which to do common garden experiments, and 3) the ability to measure virulence and key fitness components such as transmission potential in these experiments. The virus IHNV is one of the few pathogens that meet these requirements. IHNV has been both endemic and epidemic in many salmonid fish populations of the Pacific Northwest since the 1950s, and made two independent host jumps into rainbow trout. This research will utilize a collection of 3000 IHNV isolates that covers the two host jump events and five subsequent decades to pursue four research foci. (1) Experimental determination of viral virulence throughout emergence (2) Experimental determination of viral transmission potential throughout emergence. (3) Whole genome sequencing to determine genetic correlates of virulence and transmission potential. (4) Mathematical modeling to dissect the selective forces driving virulence evolution and assess the evolutionary risks of environmental change. The research is expected to show that interactions between virulence, transmission potential, and the ecological setting can be used to explain changes in the virulence of an emerging pathogen over time.

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.