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Principal Investigator: Arinjay Banerjee
Organization: WASHINGTON STATE UNIVERSITY
Fiscal Year: 2022
Award: $170,173
Funding agency: National Institute of Allergy and Infectious Diseases
Assessing the interferome of novel, purpose-driven bat-derived cells
SUMMARY/ABSTRACT
Over the last decade, bats have emerged as intriguing mammalian reservoirs of emerging high
impact viruses that cause severe disease in humans and agricultural animals. However, bats that are
naturally or experimentally infected with these viruses do not develop clinical signs of disease. Thus,
understanding how bats tolerate virus infections may allow us to develop novel drugs or identify new
drug targets for alternate mammalian species, such as humans. In spite of recent advances in bat
immunology, studies have largely relied on cell culture models from selected bat species, limiting our
understanding of this diverse mammalian order. The order Chiroptera is made up of over 1420 species
of bats, and data from a handful of bats do not represent evolutionary adaptations in all bats. In addition,
these reagents are not available on public repositories making it hard for the research community to
pursue this intriguing and growing field of research.
For our proposal, we propose to develop novel bat reagents, including primary and immortalized
cells from five major bat species, Rousettus aegyptiacus, Pteropus alecto, Eptesicus fuscus, Artibeus
jamaicensis, and Carollia perspicillata, representing bats that currently exist in research colonies,
making future in vivo translational studies feasible and logical. Data from selected bats, such as
Rousettus, Pteropus and Eptesicus bats suggest that bat cells have evolved adaptations in their
cytokine responses to better tolerate virus infections relative to humans. Type I interferon (IFN)
responses are the first line of mammalian antiviral defense, and although type I IFNs and their
downstream effects have been studied in selected bat cells, global cellular responses and the full range
of IFN-mediated antiviral effects or the ‘interferome’ remain elusive. For this project, we shall use our
diverse bat cell types, derived from multiple bat species, to identify and delineate evolutionarily
conserved and unique bat-specific IFN responses. Results from our study will shed light on intriguing
questions around the ability of bats to control infection with zoonotic RNA viruses, along with making
important discoveries on evolutionary adaptations in the mammalian type I IFN pathway. Importantly,
our research will generate critical bat reagents, such as primary cells, cell lines, recombinant cytokines
and molecular assays that will facilitate the development of larger collaborative projects to study bat
immunology.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Agriculture><Animals><Assay><Bats><Bioassay><Biologic Assays><Biological Assay><Body Tissues><Brain><Brain Nervous System><COVID-19 virus><COVID19 virus><Cell Body><Cell Culture Techniques><Cell Line><CellLine><Cells><Chiroptera><Clinical><Clone Cells><CoV-2><CoV2><Collection><Communities><Comparative Study><Competence><Complement Receptor><Coronaviridae><Coronavirus><Critical Paths><Critical Pathways><Culturing, in vitro Vertebrate, Primary><Data><Development><Disease><Disorder><Encephalon><Feasibility Studies><Future><Genus Pteropus><Goals><Hemagglutinating Virus of Japan><Human><IFN><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Immunology><Infection><Infection Control><Innate Immune Response><Innate Immunity><Interferon Type I><Interferons><Investigators><Kidney><Kidney Urinary System><Knowledge><Laboratories><Light><Liver><Lung><Lung Respiratory System><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Mediating><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome-CoV><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome-CoV><Modeling><Modern Man><Molecular><Native Immunity><Natural Immunity><Nipah Virus><Non-Specific Immunity><Nonspecific Immunity><Pathway interactions><Photoradiation><Poly I-C><Polyinosinic-Polycytidylic Acid><Predisposition><Primary Cell Cultures><Process><Pteropus><RNA Viruses><Reagent><Recombinant Cytokines><Recombinants><Reporter><Research><Research Personnel><Researchers><Resistance><Rousettus><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CO-V2><SARS-COVID-2><SARS-CoV><SARS-CoV-1><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sendai virus><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 CoV 2><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><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 corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Spleen><Spleen Reticuloendothelial System><Strains Cell Lines><Susceptibility><Testing><Therapeutic><Tissues><Tropism><VSV><Vesicular Stomatitis Virus><Vesicular stomatitis Indiana virus><Viral><Viral Diseases><Viral Receptor><Virus><Virus Diseases><Virus Receptors><Virus Replication><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><agricultural><anti-viral immunity><antiviral immunity><base><bat-borne><batborne><beta CoV><beta coronavirus><betaCoV><betacoronavirus><cell culture><cell culture collection><cell cultures><cell immortalization><cell type><corona virus><coronavirus disease 2019 virus><coronavirus disease-19 virus><cultured cell line><cytokine><developmental><experience><global health><hCoV19><hepatic body system><hepatic organ system><in vitro Model><in vivo><innate immune pathways><nCoV2><new drug target><new drug treatments><new druggable target><new drugs><new pharmacotherapy target><new therapeutic target><new therapeutics><new therapy><new therapy target><next generation therapeutics><novel><novel drug target><novel drug treatments><novel druggable target><novel drugs><novel pharmacotherapy target><novel therapeutic target><novel therapeutics><novel therapy><novel therapy target><particle><pathogen><pathogenic virus><pathway><poly IC><public repository><publicly accessible repository><publicly available repository><pulmonary><renal><resistant><response><severe acute respiratory syndrome-CoV><tool><translational study><viral infection><viral multiplication><viral pathogen><viral replication><virus infection><virus multiplication><virus pathogen><virus-induced disease><β CoV><β coronavirus><βCoV>