Date of Award
Spring 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Microbiology
First Advisor
Kumar, Priti
Abstract
The declaration of the COVID-19 pandemic compelled urgent research into better understanding the causative agent, SARS-CoV-2, and the race for a vaccine and therapeutics for the severely ill. Since its emergence in late 2019, several variants of concern have arisen, characterized in part by their mutations in the spike glycoprotein, that have altered ACE-2 binding efficiency, disease progression and pathogenesis, and viral kinetics. These mutations can also allow for immune evasion from antibodies, highlighting the need to better understand the immune response to infection and a rapid modality to characterize emerging variant pathogenesis and screen potential therapeutics. Here, we introduce a whole-body imaging system utilizing recombinant SARS-CoV-2 VOCs expressing nanoluciferase to monitor disease progression and efficacy of therapeutics. In addition, we introduce a new, immunodeficient mouse strain, the NSG ROSA26-K18-hACE2, that develops robust disease with the less pathogenic SARS-CoV-2-Omicron variant, and can serve as a murine model for the less pathogenic variants of concern.
Recommended Citation
Symmes, Kelly, "Visualization of Infection and Therapies for SARS-CoV-2 Variants of Concern in Murine Models of Infection" (2023). Yale Graduate School of Arts and Sciences Dissertations. 1197.
https://elischolar.library.yale.edu/gsas_dissertations/1197
