The goal of this project is to understand the immune response in bats infected experimentally with SARS-CoV-2. Bats are the natural reservoirs of hundreds of coronaviruses, including SARS-CoV-2, the virus that causes COVID-19 disease. It is evident that infection of bats with these viruses does them no harm, yet the viruses are capable of replicating and transmitting to other bats. Unfortunately, some of these viruses can spill over into humans and cause disease outbreaks that lead to aggressive inflammatory immune responses that contribute to the disease. It is unclear why these viruses fail to cause disease in bats, nor how the immune systems of bats control the infection without inflammatory disease that is observed in humans. This project will examine the role of the immune system of Jamaican fruit bats experimentally infected with SARS-CoV-2 in a controlled laboratory setting. The objective of the project is to understand how bat immune systems can limit virus replication and shedding but without disease. This, in turn, may lead to a better understanding of spillover events into humans, permit novel approaches to mitigate those events, and identify new therapeutic strategies for the treatment of human disease. In addition to these therapeutic broader impacts, this project supports the training of one graduate student and the research will be disseminated by public outreach and formal science meetings.
This project will determine the roles of the innate and adaptive immune responses in bats experimentally infected with SARS-CoV-2. In humans, there is compelling evidence that much of the COVID-19 pathology is caused by the immune response that leads to pronounced inflammation due to excess cytokine production. In bats naturally infected with coronaviruses, signs of disease are not apparent and experimental challenge with virus leads to innocuous infection. Experimental infection of Jamaican fruit bats show abundant SARS-CoV-2 antigen only in the intestines, particularly in cells of the Peyer?s patches, mononuclear cells of the lamina propria, and crypt cells, yet the intestinal architecture remains nominal. Virtually nothing is known about how bats serve as reservoir hosts of coronaviruses, thus this project will provide the greatest detail yet on how bats control viruses that cause substantial disease burden in humans. The project aims to achieve three objectives with SARS-CoV-2-infected bats: (1) disabling of the type I interferon pathway to determine the role of the innate response during infection; (2) determining the immune cells of Peyer?s patches that respond during infection and which of these cells are infected; and (3) what is the role of T cells in control of the virus by impairing clonal expansion and activation. Collectively, these aims will provide the first experimental manipulation of bat immunity during infection and will define how bat immune responses control infection. This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
