Experimental infections reveal unexceptional viral tolerance in bats

Bats are a conspicuous source of zoonotic viruses with pandemic potential. A common explanation for bats being ‘special’ viral reservoirs is their ability to coexist with viruses without suffering overt disease. This assumption has catalyzed extensive research into the nature of bats as viral reservoirs and aspirations to develop novel therapeutics for humans based on unique features of bat immune systems that endow bats with broad viral tolerance. Surprisingly, the ubiquitous belief that bats evolved generalized viral tolerance mechanisms derives from relatively few well studied host-virus interactions rather than comprehensive analysis of globally available data. Here, synthesizing eighty-six years of experimental infections, involving 54 viruses, 85 host species, and over 5,600 individuals, we show that viral tolerance in bats appears unexceptional, with severe disease following inoculation by taxonomically diverse viruses, including ones that are relatively benign in humans. Bats’ ability to prevent or limit the extent of clinical disease was indistinguishable from rodents, another prominent zoonotic reservoir for which major life history differences were hypothesized to select for contrasting antiviral strategies. We demonstrate that infection outcomes are instead shaped by experimental design, viral host range, and evolutionary context, suggesting that bats respond to novel infections similarly to other host groups. Our results question the idea that bats possess a ‘one size fits all’ solution wherein distinctive immune features protect against a wide variety of viruses. Instead, these features are likely to either have evolved from prolonged evolutionary interactions with specific viruses or to be evolutionarily unique but not determinants of disease outcomes across diverse viruses. Developing future biomedical translations of bat immunity and identifying life history traits which predispose host species to carry high consequence zoonoses is likely to require a nuanced understanding of specific host-virus interactions.