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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
PubMed

Insights

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.
Keywords:
5′ terminal deletiongroup-B coxsackievirusinsulinpancreatitistype 1 diabetes

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