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Principal Investigator: MICHELLE L BAKER
Organization: COMMONWEALTH SCIENTIFIC & INDUST RES ORG
Fiscal Year: 2023
Award: $146,098
Funding agency: National Institute of Allergy and Infectious Diseases
Project summary/abstract
Bats are important reservoir hosts for a variety of viruses, several of which are associated with fatality rates as
high as 90% among diagnosed human cases. This includes the highly pathogenic henipaviruses, of which
Hendra virus (HeV) emerged in Australia and Nipah virus (NiV) in South-east Asia via horse and pig
intermediate hosts respectively. The henipaviruses have been shown to be transmitted from Pteropus bats,
with the Australian black flying fox (Pteropus alecto) confirmed as a reservoir for HeV (1, 2). As with other viral
infections in bats, natural or experimental infection of bats with HeV causes no clinical signs of disease despite
shedding of virus. The antiviral immune response of P. alecto is among the most well studied of all bat species,
with novel immune mechanisms already discovered including the constitutive expression of interferon alpha
discovered by our team (3). These characteristics make the P. alecto – HeV model uniquely suited to
answering the questions we propose in this project. Despite the increasing emergence of zoonotic viruses from
bats, studies of bat immunology remain in their infancy and few studies have examined the adaptive immune
responses of any bat species. Understanding the antiviral responses in bats is crucial if we are to predict and
prevent virus spillover from bats to other susceptible species, understand disease pathogenesis in other
mammals and uncover new therapeutics and vaccines to treat these diseases in humans and other animals.
In this study, we will characterise the innate and adaptive immune response of experimentally infected bats to
HeV to obtain detailed insights into how bats control viral infection. The cell mediated immune response of bats
will be dissected using functional assays to determine the subsets of cells activated during an active infection
and explore global gene and protein expression to characterise the innate and adaptive immune response of
infected bats. The use of innovative approaches to identify MHC bound HeV peptides in infected bats, building
on previous bat immunopeptidomics studies, will provide new insights into peptide presentation during
infection. Few studies have comprehensively studied the immune response of bats during infection, and none
have examined the functional activation of the cell mediated immune response. Comparison with infected
ferrets will allow us to directly compare mechanisms responsible for innocuous (bats) compared to fatal
(ferrets) HeV infection. Expected outcomes include understanding the basic biology of antiviral responses in
bats and the development of new tools to monitor bat immunity to HeV and related viruses.
The Australian Centre for Disease Preparedness and Monash University are uniquely suited for performing the
work outlined in this proposal with a strong track record of working together on bat immunology. The team has
access to high containment facilities and expertise to perform animal infections with dangerous pathogens
combined with access to protein chemistry facilities and expertise in generating tetramer reagents.
Terms: <(IFN) α><(IFN)-α><(IFN)α><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Accounting><Adaptive Immune System><Alferon><Animals><Anti-Viral Response><Antibodies><Antigenic Determinants><Antigens><Antiviral Response><Assay><Australia><Bats><Binding><Binding Determinants><Bioassay><Biologic Assays><Biological Assay><Biology><Black Flies><Blackflies><CD8><CD8B><CD8B1><CD8B1 gene><COVID-19 virus><COVID19 virus><Cell Body><Cell Mediated Immunology><Cell-Mediated Immunity><Cells><Cellular Immunity><Characteristics><Chiroptera><Clinical><Clinical Treatment Moab><CoV-2><CoV2><Containment><Dangerousness><Development><Diagnosis><Disease><Disorder><Domestic Horse><Epitopes><Equine><Equine Morbillivirus><Equine Species><Equus caballus><Equus przewalskii><Evolution><Family Pteropodidae><Family suidae><Fatality rate><Ferrets><Flying Foxes><Fossils><Generations><Genus Pteropus><Goals><Habitats><Hendra><Hendra Virus><Henipavirus><Horses><Human><IFN Alpha><IFN α><IFN-α><IFNa><IFNα><Immune><Immune response><Immune system><Immunes><Immunity><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Immunological response><Immunology><Immunology procedure><In Situ><Infection><Innate Immune Response><Interferon Alfa-n3><Interferon alpha><Interferon-α><Intervention><Intervention Strategies><LYT3><Leukocyte Interferon><Light><Lymphoblast Interferon><Lymphoblastoid Interferon><MHC Receptor><Major Histocompatibility Complex Receptor><Mammalia><Mammals><Mediating><Modeling><Modern Man><Molecular Interaction><Monitor><Monoclonal Antibodies><Nervous System Diseases><Neurologic Disorders><Neurological Disorders><Nipah Virus><Outcome><Pathogenesis><Pathogenicity><Peptide-MHC><Peptide-Major Histocompatibility Protein Complex><Peptide/MHC Complex><Peptide/Protein Chemistry><Peptides><Photoradiation><Pigs><Predisposition><Preparedness><Protein Chemistry><Proteomics><Pteropodidae><Pteropus><RNA Seq><RNA Viruses><RNA sequencing><RNAseq><Readiness><Reagent><Receptor Protein><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><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-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><Simuliidae><Southeast Asia><Southeastern Asia><Staining method><Stains><Suidae><Susceptibility><Swine><T-Cell Antigen Receptors><T-Cell Receptor><T-Cells><T-Lymphocyte><Transmission><Universities><Validation><Viral><Viral Diseases><Viral Shedding><Virus><Virus Diseases><Virus Replication><Virus Shedding><Work><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><acquired immune system><adaptive immune response><bat-borne><batborne><cell mediated immune response><constitutive expression><constitutive gene expression><coronavirus disease 2019 virus><coronavirus disease-19 virus><cytokine><developmental><flu><global gene expression><global transcription profile><hCoV19><host response><immune system response><immunogen><immunologic assay><immunologic assay/test><immunoresponse><infancy><infantile><innovate><innovation><innovative><insight><interventional strategy><mAbs><monoclonal Abs><mortality><nCoV2><nervous system disorder><neurological disease><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><new vaccines><next generation therapeutics><next generation vaccines><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><novel vaccines><pMHC><pathogen><porcine><prevent><preventing><protein expression><receptor><suid><thymus derived lymphocyte><tool><transcriptome><transcriptome sequencing><transcriptomic sequencing><transmission process><validations><viral infection><viral multiplication><viral replication><virus infection><virus multiplication><virus-induced disease>