The host response to infection is a critical determinant of virus pathogenicity. Emerging viruses require the host cellular machinery to replicate and successfully infect new hosts, and must subvert host immunity to effectively hijack host cells. The interplay between pathogen and host, and the subsequent responses induced by infection, is the battleground that determines disease phenotype and clinical outcome. Viruses induce myriad host responses, including both antiviral responses that protect the host and aberrant responses that cause damage and enhance pathogenicity. My talk focuses on my approach to understand the complexity of virus-host interactions by combining classical virology with modern systems biology approaches. A key component to this is using reliable experimental models such as the Collaborative Cross mouse systems genetics resource. We used this panel of genetically diverse mice to characterize host responses to infection, elucidate mechanisms of pathogenesis, predict disease outcome, and identify translational opportunities for therapeutic intervention in Ebola virus disease. This model is now being applied to studying SARS-CoV-2.

Learning Objectives:

1. Understanding how systems approaches can be used to investigate the role of the host response in virus pathogenesis

2. Explain the advantages and disadvantages to using different animal models to study human viral disease

3. Understand how the Collaborative Cross mouse model is useful for investigating the host response to Ebola virus infection and its role in disease pathogenesis