A natural rodent model for virus discovery and transmission reveals biological features influencing virus population dynamics

Emerging viruses represent a major threat to global health. There are few experimental models that are able to characterize virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats (which harbor a myriad of natural rodent pathogens) are co-housed with laboratory mice. This 'dirty' mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We have identified numerous viruses and other microbial species that transmit to co-housed mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families. The diverse microbial species present in pet store mice allowed us to uncover pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astrovirus during transmission to and spread within a new host. Finally, by co-housing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.