The Mucosal Lesion in Viral Enteritis: Extent and Dynamics of the Epithelial Response to Virus Invasion in Transmissible Gastroenteritis of Piglets

In transmissible gastroenteritis (TGE) of piglets, an infection closely resembling human rotavirus enteritis, we studied the timing and extent of epithelial viral invasion along the small intestine after a single oral inoculum of virus; we related these findings to measured alterations in mucosal structure, kinetics, and differentiation, and to previously documented abnormalities of ion transport that occurred at the height of diarrhea. Six and twelve hours after inoculation, before diarrhea, extensive specific viral immunofluorescence and viral particles on electron microscopy were seen in villus but not crypt enterocytes in jejunum, mid-intestine, and ileum. At 24 and 40 hr, when diarrhea was most severe, immunofluorescence was patchy; villus blunting (P < 0.001) and increased crypt depth (P < 0.001) were observed by light microscopy in all segments; radioautographically labeled enterocytes showed accelerated migration and shortened life span; and cells on villi were deficient in sucrose activity (P < 0.001) and rich in thymidine kinase activity (P < 0.005), suggesting relative immaturity. Villus structure recovered by 72 and 144 hr, although deeper crypts (P < 0.001) and accelerated migration still persisted. We conclude that extensive, almost simultaneous direct viral invasion of villus enterocytes can occur along the entire length of the small intestine after a single exposure to virus, and thus can cause shedding of mature villus cells and proliferation and accelerated migration of cells from the crypts. At the height of diarrhea, when enterocyte turnover is maximal, the epithelium consists predominantly of immature virus-free cells which have migrated to the villi in a relatively undifferentiated state.