ArticlePLoS pathogens2011
Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 183 citations in OpenAlex.
- Identifying risk factors for vomiting during diarrhea: A secondary analysis of a randomized trial of zinc supplementation.Journal of pediatric gastroenterology and nutrition · 2025Trial
- Ondansetron treatment reduces rotavirus symptoms-A randomized double-blinded placebo-controlled trial.PloS one · 2017Trial
- Article
- BEST4⁺ cells: a potential hub of intestinal ion transport and diarrhea manipulation.Advanced biotechnology · 2026Review
- Proliferative Cell Targeting and Epithelial Cell Turnover Fuels Hepatitis E Virus Replication in Human Intestinal Enteroids.Gastro hep advances · 2026Article
- TREM-1 Interacts with Rotavirus Proteins and Drives Inflammatory Responses: A Combined Experimental and Computational Approach.Pathogens (Basel, Switzerland) · 2025Article
- Sensory signals for nausea.Trends in neurosciences · 2025Review
- Rotavirus Infections: Pathophysiology, Symptoms, and Vaccination.Pathogens (Basel, Switzerland) · 2025Review
- Innate immune sensing of rotavirus by intestinal epithelial cells leads to diarrhea.Cell host & microbe · 2025Article
- Loss of mucin 2 and MHC II molecules causes rare resistance to murine RV infection.Journal of virology · 2025Article
- Neural pathways of nausea and roles in energy balance.Current opinion in neurobiology · 2025Review
- Geographic disparities impacting oral vaccine performance: Observations and future directions.Clinical and experimental immunology · 2025Review
- Article
- Human norovirus disturbs intestinal motility and transit time through its capsid proteins.PLoS pathogens · 2024Article
- Review
- The protective role of prebiotics and probiotics on diarrhea and gut damage in the rotavirus-infected piglets.Journal of animal science and biotechnology · 2024Review
- Microbiota-Derived Extracellular Vesicles as a Postbiotic Strategy to Alleviate Diarrhea and Enhance Immunity in Rotavirus-Infected Neonatal Rats.International journal of molecular sciences · 2024Article
- Review
- Microbiota do not restrict rotavirus infection of colon.Journal of virology · 2023Article
- Enteric nervous system as a target and source of SARS-CoV-2 and other viral infections.American journal of physiology. Gastrointestinal and liver physiology · 2023Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rotavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS) and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca²⁺ concentration in a human midgut carcinoid EC cell line (GOT1) and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP₃), but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT₃ receptor antagonists.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.