UNLABELLED: Astroviruses are a common cause of gastrointestinal disease in humans and have been linked to fatal cases of encephalitis. A major barrier to the study of human-infecting astroviruses is the lack of an IMPORTANCE: Astroviruses routinely cause infections in humans
however, few methods were available to study these viruses. Here, we describe the first animal system to study human-infecting astroviruses by using mice. We demonstrate that mice are susceptible to astrovirus VA1, a strain that commonly infects humans and has been linked to fatal brain infections. The virus infects the heart tissue and is associated with inflammation. When mice with impaired immune systems were infected with VA1, they were found to have higher amounts of the virus in their hearts and blood. We found that VA1 can infect cells from human blood vessels of the heart, which is associated with human health. This model will enable us to better understand how astroviruses cause disease and how the immune system responds to infection. Our findings also suggest that astroviruses could be linked to cardiovascular diseases, including in humans.