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Åke Lernmark

Principal investigator

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Rationale for enteroviral vaccination and antiviral therapies in human type 1 diabetes

Author

  • Jessica L. Dunne
  • Sarah J. Richardson
  • Mark A. Atkinson
  • Maria E. Craig
  • Knut Dahl-Jørgensen
  • Malin Flodström-Tullberg
  • Heikki Hyöty
  • Richard A. Insel
  • Åke Lernmark
  • Richard E. Lloyd
  • Noel G. Morgan
  • Alberto Pugliese

Summary, in English

In type 1 diabetes, pancreatic beta cells are destroyed by chronic autoimmune responses. The disease develops in genetically susceptible individuals, but a role for environmental factors has been postulated. Viral infections have long been considered as candidates for environmental triggers but, given the lack of evidence for an acute, widespread, cytopathic effect in the pancreas in type 1 diabetes or for a closely related temporal association of diabetes onset with such infections, a role for viruses in type 1 diabetes remains unproven. Moreover, viruses have rarely been isolated from the pancreas of individuals with type 1 diabetes, mainly (but not solely) due to the inaccessibility of the organ. Here, we review past and recent literature to evaluate the proposals that chronic, recurrent and, possibly, persistent enteroviral infections occur in pancreatic beta cells in type 1 diabetes. We also explore whether these infections may be sustained by different virus strains over time and whether multiple viral hits can occur during the natural history of type 1 diabetes. We emphasise that only a minority of beta cells appear to be infected at any given time and that enteroviruses may become replication defective, which could explain why they have been isolated from the pancreas only rarely. We argue that enteroviral infection of beta cells largely depends on the host innate and adaptive immune responses, including innate responses mounted by beta cells. Thus, we propose that viruses could play a role in type 1 diabetes on multiple levels, including in the triggering and chronic stimulation of autoimmunity and in the generation of inflammation and the promotion of beta cell dysfunction and stress, each of which might then contribute to autoimmunity, as part of a vicious circle. We conclude that studies into the effects of vaccinations and/or antiviral drugs (some of which are currently on-going) is the only means by which the role of viruses in type 1 diabetes can be finally proven or disproven.

Department/s

  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2019-01-23

Language

English

Pages

744-753

Publication/Series

Diabetologia

Volume

62

Issue

5

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes
  • Infectious Medicine

Keywords

  • Antiviral therapy
  • Autoimmunity
  • Beta cells
  • Enterovirus
  • Pancreas
  • Prevention
  • Type 1 diabetes
  • Vaccine
  • Virus

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 0012-186X