An interdisciplinary and collaborative One Health approach to investigate coronavirus infection, persistence, shedding, and antiviral immunity using wild-caught and captive bat models in the Americas

Bats represent an intriguing model to study zoonotic virus-reservoir host interactions given their apparent asymptomatic co-existence with numerous zoonotic viruses, including coronaviruses that cause severe disease in humans. However, little is known about the mechanisms that enable viral tolerance in these bats and factors that promote virus replication and shedding to cause outbreaks. To address these gaps in our knowledge about the immunological control of virus persistence in bats, in Aim 1 we will characterize virus-host interactions in bat cells and in vivo. Our long-term objective is to investigate innate and intrinsic antiviral responses in bats and their role in viral persistence. Specifically, the proposed study will characterize the persistence of coronavirus in vitro and in vivo in big brown bats (Eptesicus fuscus). A combination of viral and host directed molecular assays will be performed to determine virus persistence and replication, and the associated host antiviral response. In Aim 2, longitudinal samples from temperate Eptesicus bats in North and Central America will be analyzed to determine immune markers of stress and viral shedding in wild-caught bats in the field. Data from wild-caught bats will be analyzed to identify immune proteins associated with increased viral shedding. Finally, in Aim 3, serum immune markers that are postulated to impact viral shedding, such as cortisol will be mechanistically characterized in vitro and in vivo using bat models. This research is significant because our approach will lead to a better understanding of factors that influence viral shedding and emergence of zoonotic outbreaks and pandemics. Our approach and study design will be extensible to other zoonotic reservoir hosts like rodents that carry multiple high consequence human pathogens. Finally, data from our study will inform public health and wildlife management policies to prevent future zoonotic outbreaks in humans and agricultural animals.