The Smith lab studies innate epithelial defenses against viral infection. Humans express several classes of evolutionarily conserved antimicrobial peptides, one of the most abundant of which is the defensins. Our studies focus primarily on the antiviral mechanisms of defensins and their role in the first line of host defense against adenovirus, rotavirus, and HPV. We are developing an in vivo model of enteric mouse adenoviral infection and a translational model of 3D primary human intestinal cell culture to study the antiviral activity of naturally secreted defensins. Our goal is to uncover mechanisms of innate immune control of the earliest events in virus-host interactions that impact pathogenesis.