Prevalence of Coronaviruses in Wild Rodents

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.