Primary intestinal models to study enterovirus infection. Intestinal crypts are isolated from the small intestine and plated either in Matrigel or on transwells. Crypts plated in Matrigel form a 3D structure called enteroids. When plated in Matrigel, enteroids have an “inside-out” structure, where the apical domain faces inward, and the basolateral domain is facing outward. When crypts are plated on transwells, they form a monolayer that has apical and basolateral polarity. Images shown are from crypts that were plated in Matrigel (top) or on a transwell (bottom) and stained with DAF (green) and CAR (red), which are involved in CVB attachment, uncoating, and entry.