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Rotavirus and Serotonin Cross-Talk in Diarrhoea
Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further est...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961431/ https://www.ncbi.nlm.nih.gov/pubmed/27459372 http://dx.doi.org/10.1371/journal.pone.0159660 |
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author | Bialowas, Sonja Hagbom, Marie Nordgren, Johan Karlsson, Thommie Sharma, Sumit Magnusson, Karl-Eric Svensson, Lennart |
author_facet | Bialowas, Sonja Hagbom, Marie Nordgren, Johan Karlsson, Thommie Sharma, Sumit Magnusson, Karl-Eric Svensson, Lennart |
author_sort | Bialowas, Sonja |
collection | PubMed |
description | Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNA(NSP4)) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNA(VP4), siRNA(VP6) and siRNA(VP7). Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p < 0.05) less diarrhoea, lower diarrhoea severity score and lower total diarrhoea output as compared to mock-treated mice (n = 9). Similarly, Ondansetron-treated mice had better weight gain than mock-treated animals (p < 0.05). A most surprising finding was that the serotonin receptor antagonist significantly (p < 0.05) also attenuated total viral shedding. In summary, we show that intracellularly expressed NSP4 stimulates release of serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron. |
format | Online Article Text |
id | pubmed-4961431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49614312016-08-08 Rotavirus and Serotonin Cross-Talk in Diarrhoea Bialowas, Sonja Hagbom, Marie Nordgren, Johan Karlsson, Thommie Sharma, Sumit Magnusson, Karl-Eric Svensson, Lennart PLoS One Research Article Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNA(NSP4)) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNA(VP4), siRNA(VP6) and siRNA(VP7). Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p < 0.05) less diarrhoea, lower diarrhoea severity score and lower total diarrhoea output as compared to mock-treated mice (n = 9). Similarly, Ondansetron-treated mice had better weight gain than mock-treated animals (p < 0.05). A most surprising finding was that the serotonin receptor antagonist significantly (p < 0.05) also attenuated total viral shedding. In summary, we show that intracellularly expressed NSP4 stimulates release of serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron. Public Library of Science 2016-07-26 /pmc/articles/PMC4961431/ /pubmed/27459372 http://dx.doi.org/10.1371/journal.pone.0159660 Text en © 2016 Bialowas et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bialowas, Sonja Hagbom, Marie Nordgren, Johan Karlsson, Thommie Sharma, Sumit Magnusson, Karl-Eric Svensson, Lennart Rotavirus and Serotonin Cross-Talk in Diarrhoea |
title | Rotavirus and Serotonin Cross-Talk in Diarrhoea |
title_full | Rotavirus and Serotonin Cross-Talk in Diarrhoea |
title_fullStr | Rotavirus and Serotonin Cross-Talk in Diarrhoea |
title_full_unstemmed | Rotavirus and Serotonin Cross-Talk in Diarrhoea |
title_short | Rotavirus and Serotonin Cross-Talk in Diarrhoea |
title_sort | rotavirus and serotonin cross-talk in diarrhoea |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961431/ https://www.ncbi.nlm.nih.gov/pubmed/27459372 http://dx.doi.org/10.1371/journal.pone.0159660 |
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