Experimental viral spillover across 25-million-year gap in Rodentia reveals limited viral transmission and purifying selection of a picornavirus

When a virus crosses from one host species to another, the consequences can be potentially devastating. However, animal models to empirically evaluate cross-species transmission can fail to recapitulate natural transmission routes, physiologically relevant doses of pathogens, and population structures of naturally circulating viruses. Here we present a new model of cross-species transmission where deer mice (Peromyscus maniculatis) are exposed to the natural virome of pet store mice (Mus musculus). Using RNA sequencing we track viral transmission via fecal-oral routes and find evidence of transmission of murine astroviruses, coronaviruses, and picornaviruses. Deep sequencing of Murine kobuvirus revealed tight bottlenecks during transmission and purifying selection that leaves limited diversity present after transmission from Mus to Peromyscus. This work provides a structure for studying viral bottlenecks across species while keeping natural variation of viral populations intact, and a high resolution look at within-host dynamics that occur during the initial stages of cross-species viral transmission.