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. IMPORTANCE: Increasing evidence supports microbial exposure as a critical factor in shaping responses to immune challenges such as infections and vaccinations. However, many experimental models introducing microbial exposure into laboratory animals have confounding factors that may impact phenotypes and are not well characterized. Here, we characterized the pet store reservoir virome diversity, prior infection history, and transmission kinetics. We found significant heterogeneity across these features of the pet store cohousing model. Moreover, we leveraged this model to investigate the tropism of two less characterized viruses-murine Kobuvirus and murine astrovirus 2-in a natural transmission setting. These findings highlight the importance of characterizing the virome of pet store reservoirs to better mimic microbial exposure in humans.