Antiviral T cell Responses During SARS-CoV-2 Infection

National Institute Of Allergy And Infectious Diseases

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Linked publications & trials

Abstract

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.