Expression of Human Decay-Accelerating Factor on Intestinal Epithelium of Transgenic Mice Does Not Facilitate Infection by the

In vitro, infection of polarized human intestinal epithelial cells by coxsackievirus B3 (CVB3) depends on virus interaction with decay-accelerating factor (DAF), a receptor expressed on the apical cell surface. Althoughmice are highly susceptible to CVB3 infection when virus is delivered by intraperitoneal injection, infection by the enteral route is very inefficient. Murine DAF, un-like human DAF, does not bind virus, and we hypothesized that the absence of an accessible receptor on the intestinal surface is an important barrier to infection by the oral route. We generated transgenic mice that express human DAF specifically on intes-tinal epithelium andmeasured their susceptibility to infection by a DAF-binding CVB3 isolate. Human DAF permitted CVB3 to bind to the intestinal surface ex vivo and to infect polarized monolayers of small-intestinal epithelial cells derived fromDAF transgenic mice. However, expression of human DAF did not facilitate infection by the enteral route either in immunocompe-tent animals or in animals deficient in the interferon alpha/beta receptor. These results indicate that the absence of an apical re-ceptor on intestinal epithelium is not the major barrier to infection of mice by the oral route. IMPORTANCE CVB3 infection of human intestinal epithelial cells depends on DAF at the apical cell surface, and expression of human DAF on murine intestinal epithelial cells permits their infection in vitro. However, expression of human DAF on the intestinal surface of transgenic mice did not facilitate infection by the oral route. Although the role of intestinal DAF in human infection has no