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Principal Investigator: William A Schountz
Organization: COLORADO STATE UNIVERSITY
Fiscal Year: 2024
Award: $2,266,918
Funding agency: National Institute of Allergy and Infectious Diseases
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.
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Outbreaks><Disorder><EBOV><Ebola virus><Ebola-like Viruses><Encephalitis><Epidemic Parotitis><Epidermal Thymocyte Activating Factor><Equine Morbillivirus><Event><FLT 3 Ligand><FLT3 ligand><FLT3L><FLT3LG><FLT3LG gene><FMS-Related Tyrosine Kinase 3 Ligand Gene><FMS-Related Tyrosine Kinase-3 Ligand><Family Pteropodidae><Filoviridae><Filovirus><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Flying Foxes><Frankfurt-Marburg Syndrome Virus><Freezing><Future><GM-CSF><Genus Pteropus><Granulocyte-Macrophage Colony-Stimulating Factor><HCV><Health><Hendra Virus><Hendra henipavirus><Henipavirus><Henipavirus Infections><Hepatitis C virus><Histamine-Producing Cell-Stimulating Factor><Human><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><IL-2><IL-4><IL2 Protein><IL4 Protein><Immune><Immune Interferon><Immune response><Immunes><Immunologic Surface Markers><Immunological Surface Markers><Immunological response><Immunology><In 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2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><STK1-ligand><Sarbecovirus><Severe Acute Respiratory Coronavirus><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome coronavirus disease><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Strains Cell Lines><Study models><Surface Antigens><Susceptibility><T cell growth factor><T-Cell Growth Factor><T-Cell Growth Factor 2><T-Cell Stimulating Factor><T-Cells><T-Lymphocyte><TC-GM-CSF><Testing><Therapeutic><Thymocyte Stimulating Factor><Tissues><Tumor-Cell Human GM Colony-Stimulating Factor><Universities><Veiled Cells><Viral><Viral Diseases><Virus><Virus Diseases><Work><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><adaptive immune response><bat-borne><batborne><beta CoV><beta coronavirus><betaCoV><betacoronavirus><biobank><biorepository><cell culture><cell cultures><cell immortalization><corona virus><coronavirus disease 2019 virus><coronavirus disease therapy><coronavirus disease treatment><coronavirus disease-19 virus><coronavirus therapy><coronavirus treatment><cultured cell line><cytokine><deep sequencing><detection assay><developmental><epidemic parotiditis><experiment><experimental research><experimental study><experiments><flk2 ligand><flk2-flt3 ligand><flow cytophotometry><flt3 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