title: Expression of human decay-accelerating factor on intestinal epithelium of transgenic mice does not facilitate infection by the enteral route.
abstract: 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. Although mice are highly susceptible to CVB3 infection when virus is delivered by intraperitoneal injection, infection by the enteral route is very inefficient. Murine DAF, unlike 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 intestinal epithelium and measured 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 from DAF transgenic mice. However, expression of human DAF did not facilitate infection by the enteral route either in immunocompetent animals or in animals deficient in the interferon alpha/beta receptor. These results indicate that the absence of an apical receptor on intestinal epithelium is not the major barrier to infection of mice by the oral route.
  
  
  OBJECTIVE
  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 not been directly examined, these results suggest that DAF is not the critical factor in mice.
authors: Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: Jieyan
authors: J
authors: Pan
authors: Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: Lili
authors: L
authors: Zhang
authors: Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
authors: Matthew A
authors: MA
authors: Odenwald
authors: Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
authors: Le
authors: L
authors: Shen
authors: Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
authors: Jerrold R
authors: JR
authors: Turner
authors: Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA bergelson@email.chop.edu.
authors: Jeffrey M
authors: JM
authors: Bergelson
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004198:Disease Susceptibility / Q000821:virology*; D029822:Enterovirus B, Human / Q000502:physiology*; D004769:Enterovirus Infections / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018958:CD55 Antigens; D017931:DNA Primers
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