Date of Award

2024-08-01

Degree Name

Doctor of Philosophy

Department

Biosciences

Advisor(s)

Hugues Ouellet

Abstract

Considering that the number of SARS-CoV-2 cases and deaths continues to increase three years after the onset of the pandemic, the need for animal models to study disease pathology and test antiviral effectiveness remains paramount. Prairie voles offer unique advantages as an infection model, such as mirroring human social behavior, including pair bonding and biparental offspring rearing, having inducible estrus and ovulation cycles, and not being overly domesticated. Based on the sequence homology of the vole ACE2 receptor to that of other species that are susceptible to SARS-CoV-2, such as the ferret and hamster, we hypothesized that the vole ACE2 receptor would bind to the receptor binding domain (RBD) within the Spike protein of SARS-CoV-2. Using VSV pseudoparticles expressing the Spike protein, we determined that the vole ACE2 receptor facilitated viral entry. Intranasal and aerosol inoculation of the voles resulted in a peak in viral RNA levels in the lungs of the animals 4 dpi. Additionally, at 7 dpi, we observed viral RNA levels in the lungs, brain, and nasal wash of uninfected voles housed with an infected cage mate. Viral RNA levels detected in the voles following either inoculation method were comparable to those observed in the K18hACE2 transgenic mouse model. Finally, we observed a significant reduction in both viral RNA copies and titer following treatment of SARS-CoV-2 infected voles with remdesivir. Our findings demonstrate that the prairie voles are susceptible to SARS-CoV-2 infection, can transmit the virus to uninfected cage-mates, and can be treated with an established antiviral.

Language

en

Provenance

Received from ProQuest

File Size

137 p.

File Format

application/pdf

Rights Holder

Stephanie Rebecca Kehl

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Included in

Virology Commons

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