Naturally transmitted mouse viruses highlight the heterogeneity of virus transmission dynamics in the dirty mouse model

Specific-pathogen-free (SPF) mice are widely used in biomedical research to model human infections. However, these animals do not always accurately recapitulate human immune responses. This is due, in part, to their lack of infection history. A growing number of studies show that the host microbiome influences the development, progression, and responses of many diseases. To date, the majority of research on the microbiome has focused on the bacterial populations and less on the eukaryotic virome of the host. Here, we characterize a transmission model where SPF mice are exposed to natural mouse pathogens at physiologic doses and routes. We found that pet store mice acquired from different sources have distinct viromes and infection histories. We also found significant heterogeneity in the kinetics of the transmission of natural mouse viruses. A common virus found in our model was murine Kobuvirus. Surprisingly, murine Kobuvirus infection was found in the glandular stomach epithelia and not intestinal epithelia like other enteric picornaviruses. Together, these data characterize the heterogeneity of the dirty mouse cohousing system and provide a foundation for studying the biology of natural mouse viruses.