Lessons learned from bat and rodent reservoir hosts of zoonotic viruses

Zoonotic virus emergence is a continued threat to global health, though more than two-thirds originate in wildlife. Within natural reservoirs, bats and rodents are host to a remarkable diversity of highly pathogenic viruses, including coronaviruses, filoviruses, hantaviruses, and more. Yet, reservoir hosts rarely develop disease. In bats, functional adaptations related to inflammasome activation, cell death, and cytokine storm have been noted, while maintaining potent interferon and restriction factor activity. Similarly, in rodent reservoirs, chronic infection with hantaviruses is associated with regulatory T cell-driven immunomodulation and subdued endothelial responses. Moving forward, integrating genomic surveillance, ecological data, and artificial intelligence will transform the identification of unknown reservoirs, predict spillover risk, and accelerate the discovery of antivirals.