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Replication Activities of Major 5' Terminally Deleted Group-B Coxsackievirus RNA Forms Decrease PCSK2 mRNA Expression
Domitille Callon1,2, Aurélien Guedra1,2, Anne-Laure Lebreil1
1Cardiovir EA-4684, Faculty of Medicine, University of Reims Champagne Ardennes, 51 Rue Cognacq Jay, 51097 Reims, France.
Viruses
|December 23, 2022
Summary
Emergence of 5' terminally deleted coxsackievirus-B RNA (CVB-TD) replicative forms in pancreatic beta cells impairs insulin secretion, potentially driving type 1 diabetes development.
Area of Science:
- Virology
- Immunology
- Endocrinology
Background:
- 5' terminally deleted coxsackievirus-B RNA (CVB-TD) forms are linked to human diseases.
- Their impact on insulin metabolism and diabetes development is unknown.
Purpose of the Study:
- To investigate the role of CVB-TD RNA replication in pancreatic beta cells and its effect on insulin metabolism.
- To determine the potential link between CVB-TD and type 1 diabetes pathogenesis.
Main Methods:
- Used an immunocompetent mouse model of CVB3/28 infection to study acute and persistent CVB-TD infections.
- Analyzed viral protein expression, beta cell insulin content, and PCSK2 mRNA levels in infected pancreases.
- Transfected cultured rodent pancreatic beta cells with synthetic CVB-TD50 RNA to assess viral replication effects.
Main Results:
- CVB-TD populations were detected in mouse pancreases during acute and persistent infections, causing pancreatitis.
- Viral capsid protein 1 (VP1) expression correlated with decreased beta cell insulin content.
- CVB-TD infection led to reduced PCSK2 mRNA and plasma insulin levels.
- In vitro, CVB-TD RNA replication impaired insulin secretion by decreasing PCSK2 mRNA.
Conclusions:
- Replicative CVB-TD RNA forms in pancreatic beta cells play a key role in the development of type 1 diabetes.
- These viral forms directly contribute to the pathophysiological mechanisms underlying diabetes.
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