Rotavirus Infection Induces Transient Pancreatic Involution and Hyperglycemia in Weanling Mice
Rotavirus is a ubiquitous double-stranded RNA virus responsible for most cases of infantile gastroenteritis. It infects pancreatic islets in vitro and is implicated as a trigger of autoimmune destruction of islet beta cells leading to type 1 diabetes, but pancreatic pathology secondary to rotavirus...
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Public Library of Science
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152295/ |
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pubmed-41522952014-09-05 Rotavirus Infection Induces Transient Pancreatic Involution and Hyperglycemia in Weanling Mice Honeyman, Margo C. Laine, David Zhan, Yifan Londrigan, Sarah Kirkwood, Carl Harrison, Leonard C. Research Article Rotavirus is a ubiquitous double-stranded RNA virus responsible for most cases of infantile gastroenteritis. It infects pancreatic islets in vitro and is implicated as a trigger of autoimmune destruction of islet beta cells leading to type 1 diabetes, but pancreatic pathology secondary to rotavirus infection in vivo has not been documented. To address this issue, we inoculated 3 week-old C57Bl/6 mice at weaning with rhesus rotavirus, which is closely related to human rotaviruses and known to infect mouse islets in vitro. Virus was quantified in tissues by culture-isolation and enzyme-linked immunosorbent assay. A requirement for viral double stranded RNA was investigated in toll-like receptor 3 (TLR3)-deficient mice. Cell proliferation and apoptosis, and insulin expression, were analyzed by immunohistochemistry. Following rotavirus inoculation by gavage, two phases of mild, transient hyperglycemia were observed beginning after 2 and 8 days. In the first phase, widespread apoptosis of pancreatic cells was associated with a decrease in pancreas mass and insulin production, without detectable virus in the pancreas. These effects were mimicked by injection of the double-stranded RNA mimic, polyinosinic-polycytidylic acid, and were TLR3-dependent. By the second phase, the pancreas had regenerated but islets were smaller than normal and viral antigen was then detected in the pancreas for several days. These findings directly demonstrate pathogenic effects of rotavirus infection on the pancreas in vivo, mediated initially by the interaction of rotavirus double-stranded RNA with TLR3. Public Library of Science 2014-09-02 /pmc/articles/PMC4152295/ /pubmed/25181416 http://dx.doi.org/10.1371/journal.pone.0106560 Text en © 2014 Honeyman 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Honeyman, Margo C. Laine, David Zhan, Yifan Londrigan, Sarah Kirkwood, Carl Harrison, Leonard C. |
| spellingShingle |
Honeyman, Margo C. Laine, David Zhan, Yifan Londrigan, Sarah Kirkwood, Carl Harrison, Leonard C. Rotavirus Infection Induces Transient Pancreatic Involution and Hyperglycemia in Weanling Mice |
| author_facet |
Honeyman, Margo C. Laine, David Zhan, Yifan Londrigan, Sarah Kirkwood, Carl Harrison, Leonard C. |
| author_sort |
Honeyman, Margo C. |
| title |
Rotavirus Infection Induces Transient Pancreatic Involution and Hyperglycemia in Weanling Mice |
| title_short |
Rotavirus Infection Induces Transient Pancreatic Involution and Hyperglycemia in Weanling Mice |
| title_full |
Rotavirus Infection Induces Transient Pancreatic Involution and Hyperglycemia in Weanling Mice |
| title_fullStr |
Rotavirus Infection Induces Transient Pancreatic Involution and Hyperglycemia in Weanling Mice |
| title_full_unstemmed |
Rotavirus Infection Induces Transient Pancreatic Involution and Hyperglycemia in Weanling Mice |
| title_sort |
rotavirus infection induces transient pancreatic involution and hyperglycemia in weanling mice |
| description |
Rotavirus is a ubiquitous double-stranded RNA virus responsible for most cases of infantile gastroenteritis. It infects pancreatic islets in vitro and is implicated as a trigger of autoimmune destruction of islet beta cells leading to type 1 diabetes, but pancreatic pathology secondary to rotavirus infection in vivo has not been documented. To address this issue, we inoculated 3 week-old C57Bl/6 mice at weaning with rhesus rotavirus, which is closely related to human rotaviruses and known to infect mouse islets in vitro. Virus was quantified in tissues by culture-isolation and enzyme-linked immunosorbent assay. A requirement for viral double stranded RNA was investigated in toll-like receptor 3 (TLR3)-deficient mice. Cell proliferation and apoptosis, and insulin expression, were analyzed by immunohistochemistry. Following rotavirus inoculation by gavage, two phases of mild, transient hyperglycemia were observed beginning after 2 and 8 days. In the first phase, widespread apoptosis of pancreatic cells was associated with a decrease in pancreas mass and insulin production, without detectable virus in the pancreas. These effects were mimicked by injection of the double-stranded RNA mimic, polyinosinic-polycytidylic acid, and were TLR3-dependent. By the second phase, the pancreas had regenerated but islets were smaller than normal and viral antigen was then detected in the pancreas for several days. These findings directly demonstrate pathogenic effects of rotavirus infection on the pancreas in vivo, mediated initially by the interaction of rotavirus double-stranded RNA with TLR3. |
| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152295/ |
| _version_ |
1613130256344940544 |