Rotavirus and Serotonin Cross-Talk in Diarrhoea

Area of Science:

• Gastroenterology
• Virology
• Pharmacology

Background:

• Rotavirus (RV) infects enterochromaffin (EC) cells, stimulating serotonin secretion.
• The specific viral protein responsible for this effect and serotonin's clinical role in RV infection require identification.

Purpose of the Study:

• Identify the rotavirus protein responsible for serotonin secretion.
• Establish the role of serotonin in rotavirus-induced diarrhea.
• Evaluate the therapeutic potential of blocking serotonin receptors in rotavirus infection.

Main Methods:

• Used siRNA to silence rotavirus non-structural protein 4 (NSP4) in infected human EC tumor cells.
• Correlated intracellular calcium mobilization and diarrheal capacity with serotonin release using porcine rotavirus strains.
• Administered serotonin to infant and adult mice to assess diarrhea response.
• Blocked serotonin receptors with Ondansetron in infant mice infected with murine rotavirus (EDIM strain) to evaluate diarrhea and viral shedding.

Main Results:

• siRNA targeting NSP4 significantly reduced serotonin secretion from infected EC tumor cells.
• Serotonin administration induced diarrhea in infant mice but not adult mice.
• Ondansetron treatment significantly attenuated rotavirus diarrhea duration, severity, and output in infant mice.
• Ondansetron treatment improved weight gain and significantly reduced viral shedding in infected mice.

Conclusions:

• Intracellularly expressed NSP4 stimulates serotonin release from human EC tumor cells.
• Serotonin plays a significant role in rotavirus-induced diarrhea.
• Blocking serotonin receptors with Ondansetron is a potential therapeutic strategy for rotavirus infections, reducing diarrhea and viral shedding.