Hamsters Expressing Human Angiotensin-Converting Enzyme 2 Develop Severe Disease following Exposure to SARS-CoV-2
Joseph W. Golden, Rong Li, Curtis R. Cline, Xiankun Zeng, Eric M. Mucker, Amadeo J. Fuentes-Lao, Kristin Spik, Janice A. Williams, Nancy Twenhafel, Neil M. Davis, Joshua L. Moore, Stephen Stevens, Eugene Blue, Aura R. Garrison, Deanna Larson, Rebekah Stewart, Madelyn Kunzler, Yanan Liu, Zhongde Wang, Jay W. Hooper
Abstract
The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human SARS-CoV-2 disease is mild, some people develop severe, life-threatening disease. Small-animal models mimicking the severe aspects of human disease are needed to more clearly understand the pathophysiological processes driving this progression. Here, we studied SARS-CoV-2 infection in hamsters engineered to express the human angiotensin-converting enzyme 2 viral receptor under the control of the K18 promoter. SARS-CoV-2 produces a severe and lethal infection in transgenic hamsters that mirrors the most severe aspects of COVID-19 in humans, including respiratory and neurological injury. In contrast to other animal systems, hamsters manifest disease with levels of input virus more consistent with natural human infection. This system will be useful for the study of SARS-CoV-2 disease and the development of drugs targeting this virus.