Astroviruses are non-enveloped, single-stranded RNA viruses that infect mammalian and avian species. In humans, astrovirus infections are one of the most common causes of gastroenteritis in children. Infection has also been linked to serious neurological complications, especially in immunocompromised individuals. More extensive disease has also been characterized in non-human mammalian and avian species. To date, astroviruses have been detected in over 80 different avian and mammalian hosts. As the number of hosts continues to rise, the need to understand how astroviruses transmit within a given species as well as to new host species becomes increasingly important. Here, we review the current understanding of astrovirus transmission, the factors that influence viral spread, and the potential for cross-species transmission. Additionally, we highlight the current gaps in knowledge and areas of future research that will be key to understanding astrovirus transmission and zoonotic potential.

Influenza viruses pose a significant burden on global human health. Influenza has a broad cellular tropism in the airway, but how infection of different epithelial cell types impacts replication kinetics and burden in the airways is not fully understood. Using primary human airway cultures, which recapitulate the diverse epithelial cell landscape of the human airways, we investigated the impact of cell type composition on virus tropism and replication kinetics. Cultures were highly diverse across multiple donors and 30 independent differentiation conditions and supported a range of influenza replication. Although many cell types were susceptible to influenza, ciliated and secretory cells were predominantly infected. Despite the strong tropism preference for secretory and ciliated cells, which consistently make up 75% or more of infected cells, only ciliated cells were associated with increased virus production. Surprisingly, infected secretory cells were associated with overall reduced virus output. The disparate response and contribution to influenza virus production could be due to different pro- and antiviral interferon-stimulated gene signatures between ciliated and secretory populations, which were interrogated with single-cell RNA sequencing. These data highlight the heterogeneous outcomes of influenza virus infections in the complex cellular environment of the human airway and the disparate impacts of infected cell identity on multiround burst size, even among preferentially infected cell types.

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats—which harbor natural rodent pathogens—are cohoused with laboratory mice. This “dirty” mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing 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.

The bacterial microbiome has a major impact on health and can shape metabolism, host tolerance, immune responses, and the outcome of future infections. The bacterial microbiome is highly variable between individuals. Specific pathogen-free animals have reduced microbiome diversity, making it difficult to evaluate the impact of infection-induced microbiome disruption that would be observed in free-living animals, including people. Mice are commonly used as a preclinical model but unfortunately often fail to predict translation success or failure, particularly for immune and infectious disease-targeting therapies. Here, we utilize pet store mouse cohoused “dirty” mice with diverse microbial experience to explore how host variability and infection may be interacting to drive unique microbiome changes. We found that cohoused animals had significantly increased bacterial diversity in the small intestine and cecum but not in the large intestine. There were differentially abundant taxa between clean and dirty animals in all three tissues. After infection with influenza A virus, samples clustered by both housing condition and infection status in the cecum and large intestine, while small intestine samples clustered predominantly by infection. Altogether, these results highlight the differential impact of housing, infection, and interaction between the two in dictating community composition across the gastrointestinal microbiome. IMPORTANCE: Traditionally housed pathogen-free mouse models do not fully capture the natural variability observed among human microbiomes, which may underlie their poor translationally predictive value. Understanding the difference between pathogen-induced shifts in the bacterial microbiome and natural microbiome variance is a major hurdle to determining bacterial biomarkers of disease. It is also critical to understand how diverse baseline microbiomes may be differentially impacted by infection and contribute to disease. Pet store cohoused “dirty” mice have diverse microbial experiences and microbiomes, allowing us to evaluate how baseline variation, infection, and interaction between the two impact the microbiome.