Single-cell transcriptomics reveals murine astrovirus preferentially infects actively secreting goblet cells

Astroviruses are a global cause of diarrheal illness, but they are largely understudied, and it is unclear how and where they replicate in the gut. To fill this knowledge gap, we developed a murine model to study astrovirus pathogenesis. We show here that murine astrovirus infects goblet cells, specialized epithelial cells that maintain the mucus barrier, and co-opts the secretory pathway to promote its replication. Consequently, increased mucus production in the gut led to increased mucus-associated bacterial communities and resistance to enteropathogenic E. coli colonization. These studies highlight a novel pathway by which enteric viruses manipulate host responses within the gut to promote viral replication and significantly alter mucosal immunity.