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. 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.
Significance Statement Bats are the natural reservoir hosts for zoonotic viruses that cause higher case fatality rates in humans than do viruses derived from any other mammal or bird host. Using a nested population-level and within-host modelling approach, we generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, successfully reproducing human case fatality rates from zoonoses reported in the literature. Our model provides a mechanistic explanation for the virulence of bat-borne zoonoses and a general predictive framework to forecast the virulence of cross-species viral infections from diverse mammalian hosts.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Competing interest statement: The authors have no competing interests to declare.
We have edited the model and rewritten the paper. Conclusions generally map to prior versions of this analysis; however, we find the new within-host model to be better supported, and acquisition of additional life history data has enabled us to make virulence predictions for viruses evolved in diverse mammalian orders, for which no records from the literature currently exist.
