Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses.

Summary Although chronic gastrointestinal dysmotility syndromes are a common worldwide health problem, underlying 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 diminished 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 exacerbated 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. Graphical Abstract Highlights • Infection with multiple flaviviruses causes delayed gastrointestinal transit • Dysmotility and neuronal death are caused by infiltrating antiviral CD8+ T cells • Surviving animals exhibit long-term chronic gastrointestinal dysmotility • Chronic dysmotility is exacerbated by exposure to unrelated inflammatory stimuli Damage caused to enteric neurons during acute flavivirus infections manifests in the form of gastrointestinal motility abnormalities that are exacerbated in later life upon challenge with either unrelated infectious or non-infectious inflammatory stimuli. [ABSTRACT FROM AUTHOR]