Image credit: University of Pennsylvania
Infection with a common virus known as coxsackievirus B has long been thought to be associated with the development of type 1 diabetes. Now, researchers have published evidence that this virus could be driving the activity of the very genes that increase the risk of developing type 1 diabetes.
The coxsackie B virus (CBV) belongs to the enterovirus (EV) family, which are responsible for a range of human diseases including the common cold and meningitis. Viruses in this family are known to interfere with microRNAs (miRNAs), many of which regulate gene activity in insulin-producing beta cells. miRNAs are short sequences of code that are similar to DNA, but do not code for genes in the way that DNA does. Instead, they reduce the “expression” of specific genes by blocking production of the protein that the gene codes for.
In this study, researchers looked at whether CBV infection could affect miRNAs in pancreatic islet cells, and so change the expression of genes associated with T1D.
Pancreatic islet cells from two organ donors were extracted and multiplied in the laboratory. The islet cells from one of the donors were infected with CBV, while those from the other were left uninfected. After seven days, the researchers examined the levels of 754 different miRNAs in the islet cells of both donors, and found significantly changed levels of 33 miRNAs in the islet cells that had been infected with CBV.
To see if these changes could be affecting T1D risk, the researchers then looked to the genes that the miRNAs regulate. They found that the 33 miRNAs regulate 57 known risk genes of T1D, many of which are involved in inflammation and immunity. In most cases, CBV infection reduced the levels of the miRNAs in islets, potentially increasing the activity of T1D-associated genes and driving inappropriate inflammation and beta-cell death.
This study is the very first study to examine miRNA expression in CVB-infected human islets, and provides a possible mechanism for how infection with a common virus could trigger the development of T1D in people who are genetically at-risk. The study was published in leading journal Diabetes, and was led by T1DCRN researchers Professor Maria Craig from the Children’s Hospital in Westmead, Professor Tom Kay from St Vincent’s Institute in Melbourne, Associate Professor Anand Hardikar from the NHMRC Clinical Trials Centre, and their research teams.
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