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Prospective virome analyses in young children at increased genetic risk for type 1 diabetes

Kendra Vehik1, Kristian F Lynch2, Matthew C Wong3

  • 1Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. kendra.vehik@epi.usf.edu.

Nature Medicine
|December 4, 2019
PubMed

Insights

Prolonged enterovirus B infections, not short-term ones, may contribute to islet autoimmunity in children. Fewer early-life human mastadenovirus C infections and specific CXADR gene variants also correlated with islet autoimmunity.

Area of Science:

  • Virology
  • Immunology
  • Endocrinology

Background:

  • Viruses are linked to autoimmune destruction of pancreatic beta cells, leading to type 1 diabetes (T1D).
  • Enteroviruses can infect beta cells, and have been detected in T1D patients, but consistent links remain challenging due to viral mutation and variation.
  • Beta cells express the coxsackie and adenovirus receptor (CXADR), facilitating enterovirus entry, with varying virulence observed across serotypes.

Purpose of the Study:

  • To investigate the association between fecally shed viruses and islet autoimmunity in children.
  • To determine if specific viral infections or genetic factors correlate with the development of islet autoimmunity and T1D.

Main Methods:

  • Large-scale analysis of eukaryotic DNA and RNA viruses in stool samples from children.
  • Evaluation of fecal viral shedding in relation to islet autoimmunity markers and T1D diagnosis.
  • Assessment of correlations between early-life viral infections, CXADR gene variants, and islet autoimmunity.

Main Results:

  • Prolonged enterovirus B infections, rather than short-duration ones, were associated with islet autoimmunity development in some young children.
  • Early-life human mastadenovirus C infections were inversely correlated with islet autoimmunity.
  • The CXADR rs6517774 gene variant independently correlated with islet autoimmunity.

Conclusions:

  • Persistent enterovirus B infections may play a role in initiating islet autoimmunity in susceptible children.
  • Specific viral infections (human mastadenovirus C) and host genetic factors (CXADR rs6517774) are independently associated with islet autoimmunity.
  • Findings suggest complex interactions between viral infections, host genetics, and the development of autoimmune diabetes.

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