Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses

Although chronic gastrointestinal dysmotility syndromes are a common worldwide health problem, unuellying causes for these disorders are poorly understood. We show that flavivirus infection of enteric neurons leads to acute neuronal injury and cell death, inflammation, bowel dilation, and slowing of intestinal transit in mice. Flavivirus-primed CD8(+) T cells promote these phenotypes, as their absence dimin- ished enteric neuron injury and intestinal transit delays, and their adoptive transfer reestablished dysmotility after flavivirus infection Remarkably, mice surviving acute flavivirus infection developed chronic gastrointestinal dysmotility that was exacer- bated by immunization with an unrelated alphavirus vaccine or exposure to a non-infectious inflammatory stimulus. This model of chronic post-infectious gastrointestinal dysmotility in mice suggests that viral infections with tropism for enteric neurons and the ensuing immune response might contribute to the development of bowel motility disorders in humans. These results suggest an opportunity for unique approaches to diagnosis and therapy of gastrointestinal dysmotility syndromes.