Establishment of a Bat Resource for Infectious Disease Research

修改的项目摘要/摘要部分

Modified Project Summary/Abstract Section Project Summary / Abstract Bats are reservoirs, or suspected reservoirs, of many zoonotic viruses, including SARS, SARS2 and MERS coronaviruses, Nipah and Hendra viruses, and Ebola and Marburg viruses. Little is known about how these viruses circulate in their bat reservoirs, principally because of a lack of bat colonies that can be used for the development of experimental infection models. To address this deficiency, we will capture horseshoe bats and Indian flying foxes, respective reservoir hosts of Nipah virus and SARS-related coronaviruses, in Bangladesh where they will be quarantined and provided veterinary care as they adapt to captivity. Bats will be shipped to CSU to establish the breeding colonies as a resource for investigators who study these viruses. We will generate primary cell cultures and immortalized cell lines from various tissues and freeze live bone marrow that will be useful for studying how these viruses infect bat cells, and how the viruses may modulate the innate immune responses. Recombinant cytokines will also be produced for the research community, including those for generating macrophages and dendritic cells (GM-CSF, Flt3L), T cells (IL-2) and for in vivo modulation of the adaptive immune response (IFNγ, IL-4). Moreover, we will generate monoclonal antibodies for use in cytokine detection assays and flow cytometry of immune cell subsets and in vivo neutralization. Finally, we will perform experimental infection studies of Nipah virus, SARS-CoV-2 and the SARS-related coronaviruses, BANAL-52 and BANAL-236, to study the infection kinetics, virus distribution and transcriptomic, proteomic and metabolomic profiles of bats during infection, and escalation and resolution of the immune response. Tissues, cells and sera from naïve and infected bats will be archived in a biobank that will be made available to the research community. The establishment of this resource will lead to a better understanding of how bats host highly pathogenic viruses without disease and may shed light on events that increase spillover risks to humans. In turn, this information could lead to development of mitigation strategies to prevent future virus spillover and uncover new strategies for therapeutic treatment of coronavirus and Nipah virus diseases.