The importance of cellular-scale viral dynamics in bat reservoirs for emerging zoonotic disease

Brook, Cara E.; Boots, Mike; Chandran, Kartik; Dobson, Andrew P.; Drosten, Christian; Graham, Andrea L.; Grenfell, Bryan T.; Müller, Marcel A.; Ng, Melinda; Wang, Lin-Fa; van Leeuwen, Anieke

Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats’ virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity to promote the establishment of rapidly-propagating persistent infections within-host. Rapidly-replicating viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.