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Principal Investigator: Heather Hickman
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2020
Award: $258,827
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 coronavirus><2019-nCoV><Animal Model><Animal Models and Related Studies><Antiviral Agents><Antiviral Drugs><Antivirals><Body Tissues><CRE Recombinase><Cell Body><Cells><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><Disease><Disorder><Enterobacteria phage P1 Cre recombinase><Epidemic><Epithelial><Epithelium><Epithelium Part><HCoV><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><Respiratory physiology><SARS><SARS coronavirus disease><SARS-CoV disease><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome coronavirus disease><Severe acute respiratory syndrome coronavirus 2><T cell response><Tissues><Transgenic Mice><Transgenic Organisms><Wuhan coronavirus><anti-viral agents><anti-viral drugs><anti-virals><bacteriophage P1 recombinase Cre><corona virus><cytokine><human CoV><human corona virus><human coronavirus><human disease><human model><knockin mice><lung function><lymph gland><lymph nodes><lymphnodes><model of animal><model of human><model organism><mortality><mouse model><murine model><pandemic><pandemic disease><pulmonary><receptor><respiratory function><transgenic>