Researchers are still looking forwhat sets off the autoimmune response that causes type 1 diabetes, and one of the leading theories is that a virus is the culprit. In a study recently published in the Journal of the Endocrine Society, a team of investigators looked at how infecting human islets with the enterovirus coxsackievirus B4 (CVB4) could lead them to better understanding the cellular response.
The team, led by Jennifer P. Wang, MD, of University of Massachusetts Medical School in Worcester, write that clinical reports and epidemiological data support that enteroviral infections may accelerate the autoimmune disease process, and that pancreatic tissue from patients with recent-onset type 1 diabetes reveals enteroviral RNA sequences and evidence of viral proteins in islets, consistent with the possibility that low-grade infection in pancreatic islets may contribute to disease progression. The islets become infected, which sets off a strong autoimmune response, which destroys insulin-producing beta cells. “The role of virus infection in the setting of autoimmunity is still under investigation,” the authors write, “but it has become increasingly clear that an islet insult leading to local inflammation is likely central in initiating the autoimmune process.”
The researchers performed quantitative mass spectrometry analysis on cultured primary human islets infected with CVB4 to identify molecules and pathways altered upon infection. They found that once these islets were challenged with infection, insulin levels dropped considerably, which could be attributed to beta cell death. “Proteins were significantly and differentially regulated in human islets challenged with virus compared with their uninfected counterparts,” the authors write. “Complementary analyses of gene transcripts in CVB4-infected primary islets over a time course validated the induction of RNA transcripts for many of the proteins that were increased in the proteomics studies.”
The researchers conclude that this study provides additional insight on how enteroviruses may suppress human beta cells and identifies potential markers for the initiation and progression of type 1 diabetes. “Our current studies confirm the upregulation/activation of specific molecules and pathways that were previously described in clinical samples of patients with enterovirus-associated fulminant diabetes,” they write. “These molecules are potential therapeutic targets for intervention against [type 1 diabetes].”
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