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Review
. 2021 Jul 16;9(7):1519.
doi: 10.3390/microorganisms9071519.

Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

Sonia R Isaacs  1   2 , Dylan B Foskett  1   2 , Anna J Maxwell  1   2 , Emily J Ward  1   3 , Clare L Faulkner  1   2 , Jessica Y X Luo  1   2 , William D Rawlinson  1   2   3   4 , Maria E Craig  1   2   5   6 , Ki Wook Kim  1   2
Affiliations
Review

Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

Sonia R Isaacs et al. Microorganisms. .

Abstract

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, as well as mechanistic studies of virus-infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here, we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses and summarise current unbiased efforts aimed at characterising the complete population of viruses (the "virome") contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

Keywords: antiviral; coxsackievirus; enterovirus; islet autoimmunity; next-generation sequencing; type 1 diabetes; unbiased sequencing; vaccine; virome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Putative mechanisms for initiation of islet autoimmunity (IA) and acceleration to type 1 diabetes (T1D) by viruses: (1) Direct infection and β-cell cytolysis; (2) Bystander activation; (3) Dysregulation of host miRNAs; (4) Molecular mimicry; and (5) Persistent infection. These mechanisms are not mutually exclusive and likely act in interacting pathways to trigger IA and/or facilitate progression of T1D pathogenesis [107,137]. However, there is little direct mechanistic evidence from humans, with poor understanding of how virus-induced insulitis may involve into a targeted autoimmune attack [102]. Abbreviations: MHC, major histocompatibility complex.
Figure 2
Figure 2
Summary of current antiviral drugs and vaccine candidates for type 1 diabetes (T1D) prevention and potential treatment, illustrating at what stages of islet autoimmunity (IA) and T1D development these may prove useful, indicating current clinical trials aimed at preventing enterovirus infection for prevention or treatment of T1D. Abbreviations: VLP, virus-like particles; CVB, coxsackievirus B.
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