Degree
Doctor of Biomedical and Veterinary Medical Sciences-Pathobiological Sciences (PVMPB)
Department
Pathobiological Sciences
Document Type
Dissertation
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can infect a wide range of animals, including white-tailed deer (WTD). Transmission of SARS-CoV-2 to WTD raised concerns as a viral reservoir and source of continuous viral evolution. There is a significant knowledge gap regarding host-adaptive evolution in WTD, and in understanding the effects of these adaptive mutations on viral fitness, pathogenicity, and transmissibility. We performed in vitro and in vivo characterization of WTD-adaptive spike glycoprotein mutations and their effect on viral fitness, pathogenicity, and transmission. We determined that WTD-adapted spike glycoproteins showed efficient binding and entry using the host receptor (human and WTD), angiotensin-converting enzyme 2 (ACE2), and similar fusogenicity to Alpha and Delta VOCs, with the furin cleavage site mutation P681H providing marginal attenuation. Using reverse genetics, we analyzed the in vitro and in vivo growth kinetics, pathogenicity and transmissibility of two naturally occurring WTD-adapted SARS-CoV-2 strains (hCoV-19/deer/USA/OH-OSU-0343/2021, and hCoV-19/deer/Canada/ON-WTD-04658-2372/2021) corresponding to the first variants with confirmed deer-to-deer, and human spillback transmission in North America. These WTD-adapted spike variants demonstrated similar replication kinetics in non-ruminant and ruminant cell lines compared to their backbone WTD-adapted SARS-CoV-2 variant. Following intranasal infection in North American deer mice (Peromyscus maniculatus bairdii), these spike variants demonstrated no differences in pathogenicity or transmission rates. Overall, our data demonstrates that SARS-CoV-2 infection in WTD results in the accumulation of adaptive spike mutations that increase binding efficiency and entry to human and WTD ACE2 without altering their fusogenic ability, in vitro species susceptibility, or pathogenicity in Peromyscus mice.
Date
5-15-2026
Recommended Citation
Dittmar, Wellesley, "Host-Associated Evolution of SARS-CoV-2: Molecular and Virological Effects of Spike Protein Mutations Arising in North American White-Tailed Deer" (2026). LSU Doctoral Dissertations. 7087.
https://repository.lsu.edu/gradschool_dissertations/7087
Committee Chair
Carossino, Mariano
LSU Acknowledgement
1
LSU Accessibility Acknowledgment
1
Included in
Veterinary Infectious Diseases Commons, Veterinary Microbiology and Immunobiology Commons, Veterinary Pathology and Pathobiology Commons