Project Summary / Abstract
COVID-19 is caused by a bat-borne coronavirus, SARS-CoV-2, that has resulted in more than 1 million deaths
in the USA. Experimental and bioinformatic analyses suggest cricetid rodents, but not murid rodents, may be
susceptible to the virus. We determined that two such cricetid rodents, the North American deer mouse
(Peromyscus maniculatus) and California deer mouse (P. californicus) are susceptible, with some of the latter
species developing severe disease that required euthanasia. This raises the concern that spillback from
humans or susceptible domesticated animals, such as mins (Neogale vison), to North American cricetid
rodents could occur and lead to establishment of SARS-CoV-2 in secondary reservoir hosts in the New World.
Several rodent species in Europe and Asia have been found to harbor coronaviruses but, surprisingly, there
are no reports wild rodents in the New World have been examined for coronaviruses, even though they are
found in several bat species. Moreover, because of disease that occurred in California deer mice, it is possible
that it or other North American rodents could serve as new pathogenesis models for COVID-19. To examine
these possibilities, we will survey cricetid rodents in Colorado for the presence of coronaviruses, which we
have detected at a site in Utah, and generate genome sequences of these viruses for phylogenetic analysis
and important domains (e.g., protease cleavage sites). We will also determine the T cell response of deer mice
vaccinated against SARS-CoV-2 using single-cell RNA seq analysis and compared to unvaccinated deer mice.
This will lay the foundation of using deer mice as a long-lived small animal model (8 years), which cannot be
replicated with Syrian hamsters or human ACE2 laboratory mice (2 years). Together this work will determine
coronavirus diversity in North American rodents, and whether the deer mouse can serve as a durable immunity
model for SARS-CoV-2.