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Principal Investigator: Heather Hickman
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $102,819
Funding agency: National Institute of Allergy and Infectious Diseases
The emergence of SARS-CoV-2 in human populations in 2019 has resulted in a global pandemic with staggering morbidity and mortality. In humans, coronavirus-induced disease 2019 (COVID-19) is characterized by decreased lung function and increased pro-inflammatory cytokine production. As the immune mechanisms underlying COVID-19 are still being explored, small animal models of SARS-CoV-2 infection would greatly facilitate our understanding of pathogenesis post infection. SARS-CoV-2 utilizes the same receptor, human ACE2 (hACE2), as SARS for cell entry. Several small animal models were developed during the SARS epidemic that can be infected with SARS-CoV-2, allowing the rapid deployment of small animal models of SARS-CoV-2 infection. Despite this, murine models of infection have not been developed that fully capture all aspects of human COVID-19. Additionally, the broad expression of hACE2 throughout the mouse does not afford a precise determination of the importance of specific tissues during coronavirus pathogenesis. In this project, we have created stop-lox-stop-hACE2-transgenic mice. Crossing with different Cre recombinase-expressing mouse strains will allow us to systematically dissect the effect of SARS-CoV-2 infection and replication in different murine cells ranging from specific epithelial populations to immune cells. Further, we plan to analyze the antiviral T cell response when replication is restricted to different tissues. Together, these studies should inform our knowledge of SARS-CoV-2 pathogenesis and COVID-19 in humans.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ACE2><Animal Model><Animal Models and Related Studies><Body Tissues><COVID-19><COVID-19 infection><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><CRE Recombinase><CV-19><Cell Body><Cells><CoV-2><CoV2><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><Coronavirus Infectious Disease 2019><Disease><Disorder><Enterobacteria phage P1 Cre recombinase><Epidemic><Epithelium><Human><Immune><Immunes><Infection><Inflammatory><KI mice><Knock-in Mouse><Knowledge><Lung><Lung Respiratory System><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic nodes><Mice><Mice Mammals><Modern Man><Morbidity><Morbidity - disease rate><Mouse Strains><Murine><Mus><Pathogenesis><Phase><Population><Production><Receptor Protein><SARS><SARS corona virus 2><SARS coronavirus disease><SARS-CO-V2><SARS-COVID-2><SARS-CoV disease><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 pathogenesis><SARS-CoV2><SARS-CoV2 infection><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><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV disease><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 coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><T cell response><Tissues><Transgenic Mice><Transgenic Organisms><Viral><Wuhan coronavirus><angiotensin converting enzyme 2><angiotensin converting enzyme II><bacteriophage P1 recombinase Cre><corona virus><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><cytokine><hCoV19><human disease><human model><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><knockin mice><lung function><lymph gland><lymph nodes><lymphnodes><model of animal><model of human><mortality><mouse model><murine model><nCoV2><pandemic><pandemic disease><pulmonary><pulmonary function><receptor><severe acute respiratory syndrome coronavirus 2 pathogenesis><transgenic>