Bat immunology and physiology drives virulence evolution for zoonotic viruses
Monday, April 17, 2023 - 4:15pm
Icahn 101
Quantitative & Computational Biology
LSI - Genomics

Hosted by QCB Students

Talk Abstract :

The management of future pandemic risk requires a better understanding of the mechanisms that determine the virulence of emerging zoonotic viruses. Meta-analyses suggest that the virulence of emerging zoonoses is correlated with but not completely predictable from reservoir host phylogeny, indicating that specific characteristics of reservoir host immunology and life history may drive the evolution of viral traits responsible for cross-species virulence. In particular, bats host viruses that cause higher case fatality rates upon spillover to humans than those derived from any other mammal, a phenomenon that cannot be explained by phylogenetic distance alone. In order to disentangle the fundamental drivers of these patterns, we develop a nested modeling framework that pinpoints mechanisms which underpin the evolution of viral traits in reservoir hosts that cause virulence following cross-species emergence. We apply this framework to generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, successfully recapturing corresponding virus-induced human mortality rates reported in the literature. We support these findings with spatially-explicit within-host models of virus and immune dynamics fitted to in vitro data generated from experimental virus infections in diverse mammalian cell lines.  Notably, our work offers a mechanistic explanation for the extreme virulence of bat-borne zoonoses and, more generally, demonstrates how key differences in reservoir host longevity, viral tolerance, and constitutive immunity impact the evolution of viral traits that cause virulence following spillover to humans. Our theoretical framework offers a series of testable questions and hypotheses designed to stimulate future work comparing cross-species virulence evolution in zoonotic viruses derived from diverse mammalian hosts. 

Cara Brook 





Cara Brook is an Assistant Professor in the Department of Ecology and Evolution at the University of Chicago. She received her B.S. in Earth Systems from Stanford University in 2010, and her M.Sc. and Ph.D. in Ecology and Evolutionary Biology from Princeton University in 2014 and 2017, respectively, working in the lab of Professor Andy Dobson. While at Princeton, Brook pioneered a longterm fruit bat field system in Madagascar, which she maintains to this day. From 2017-2020, she was Miller Postdoctoral Fellow in the lab of Professor Mike Boots at the University of California, Berkeley, and in 2020, she was awarded a Loréal USA For Women in Science fellowship and a Branco Weiss Society in Science fellowship, which she began at Berkeley and transitioned to her current faculty job at U-Chicago.