Establishment of a Transgenic Human Angiotensin Converting Enzyme-2 Hamster Infection Model for the Evaluation of Therapeutics Against Severe Acute Respiratory Syndrome Coronavirus 2
Date of Award:
Master of Science (MS)
Animal, Dairy, and Veterinary Sciences
Brett L. Hurst (Chair), E. Bart Tarbet (Co-Chair)
Brett L. Hurst
E. Bart Tarbet
Arnaud Van Wettere
The virus SARS-CoV-2 emerged in late 2019 and has gone on to spread throughout the global population. The virus is still the cause of a healthcare crisis two years after being identified. Viral infection in humans leads to the development of the disease COVID-19. A complex disease that can result in a wide variety of outcomes for infected individuals. In the majority of individuals, COVID-19 will manifest as either an asymptomatic disease state or a mild to moderate disease state that is resolved in approximately one week. In some infected patients COVID-19 will manifest with the rapid onset of severe symptoms such as breathing difficulties. In severe cases, a marked inflammatory response results in the development of life-threatening acute respiratory distress syndrome (ARDS). In a small number of autopsies preformed on patients who died due to COVID-19, signs of encephalitis and/or stroke are observable. Neurological symptoms during infection or the development of psychiatric disorders following infection have been reported in multiple clinical reports.
To effectively combat SARS-CoV-2 spread and infection, it is crucial for us to understand the full array of disease manifestations and identify therapeutics available to combat severe infections. We have developed an animal infection model of SARS-CoV-2 in transgenic hACE2 hamsters. Virus challenge in hACE2 hamsters leads to mild to moderate clinical signs beginning ~ 2 dpi, after which symptoms quickly progress to severe as evidenced by observable difficulty breathing in hamsters. Infected hamsters succumb to SARS-CoV-2 infection at approximately 6 – 7 dpi. Infectious virus was found in lung, brain, cardiac, and renal tissue of infected hamsters. Virus titers peaked in tissues just prior to the onset of severe symptoms (~4dpi). Microscopic evaluation of hamster tissues revealed inflammation and necrosis in lung and brain tissue. Mortality in hACE2 hamsters is presumed to be the result of a combination of respiratory and neurological damage, since wild-type golden Syrian hamsters infected with SARS-CoV-2 show similar to greater pathology the lung but lack the encephalitis seen in hACE2 hamsters. Therefore, it is our conclusion that SARS-CoV-2 associated death is due in part to the neurologic pathology observed. The hACE2 hamsters model for SARS-CoV-2 infection is a model of severe SARS-CoV-2 symptomology with neurologic involvement.
Gibson, Scott A., "Establishment of a Transgenic Human Angiotensin Converting Enzyme-2 Hamster Infection Model for the Evaluation of Therapeutics Against Severe Acute Respiratory Syndrome Coronavirus 2" (2023). All Graduate Theses and Dissertations. 8699.
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