Common polymorphisms can increase the risk of acquiring complex diseases such as Crohn’s disease. We found that a viral infection triggers intestinal disease in mice with mutations in the Crohn’s disease susceptibility gene Atg16L1. This virus-plus-susceptibility gene interaction is dependent on the specific viral strain and the timing of the infection. These results provide one explanation why common gene variants are associated with disease in only a subset of individuals. The above image is a screen art of cherry blossom tree branches in which each panel represents the four experimental conditions: untreated, virus alone, gene mutation alone, and virus + gene mutation. Only the virus + gene panel shows a branch that has lost its flowers. Artwork by Marcy Hartstein.