Enterovirus Lingers in Pancreatic Cells, May Contribute to Diabetes

NEW YORK (Reuters Health) – Enterovirus-infected cells may linger in the pancreas, perhaps contributing to autoimmunity and diabetes, new research suggests.

“We have found that the pancreas carries enteroviral infection and cells were unable to clear them, causing a continuous inflammatory situation,” Dr. Kathrin Maedler of the University of Bremen, in Germany, told Reuters Health by email.

“Clinically, we need to help the immune system to clear such remaining viruses, as they may cause continuous dysfunction and destruction. This could be done with cell-directed antisense RNA-based therapies. Theoretically, one can also make vaccines against enteroviruses for diabetes therapy,” said Dr. Maedler.

Enteroviral infections are associated with autoimmunity and T1D, but reliable methods to localize single infected cells were missing, the study team explains in Cell Reports Medicine.

Using highly sensitive, single-molecule-based fluorescent in situ hybridization (smFISH) for viral RNA, Dr. Maedler and colleagues detected increased enterovirus RNA in pancreas from donors with type-1 diabetes (T1D) and disease-associated autoantibodies (AAb+), compared with control pancreas from donors without diabetes.

The proportion of donors expressing enterovirus RNA in pancreatic cells were 64% among controls (nine of 14), compared to 90% in AAb+ donors without T1D (nine of 10) and 100% among T1D donors (15 of 15).

While control pancreas harbored an average of 3.7 viral RNA-containing cells, there were 19- and 22-fold more in pancreas from AAb+ and T1D donors (average 71 and 82, respectively).

Most of the virus-positive cells were scattered within exocrine pancreas, but were also present in endocrine pancreas and immune cells. Virus-positive beta cells were rare but more often seen in T1D pancreas compared to control donor pancreas.

“The overall increased proportion of virus-positive cells in the pancreas of autoantibody-positive and T1D organ donors suggests that enteroviruses are associated with immune cell infiltration, autoimmunity and beta cell destruction in both preclinical and diagnosed T1D,” the researchers write.

“The presence of enteroviral RNA in nondiabetic AAb+ donors is in line with previous studies that have detected viral infection in children at risk for T1D. Multiple enteroviral infection rounds through early childhood may trigger the disease, and as seen here, viral sequences remain in the tissue for years after infection, having either been among the initiating or participating factors toward the damage of the pancreas and the vulnerable b cell,” they add.

“We used a broad approach to detect enteroviral RNA. We tried to narrow down this by using different detection probes, which each detect different enteroviral sequences,” Dr. Maedler told Reuters Health.

Every “time we did this, we have received some signals in the pancreas, which means that there is the possibility of various different viral infections in the past which have finally caused autoimmunity and diabetes; (this) is in line with many previous studies,” she said.

The approach used did not allow for identification of specific viral sequences. Looking ahead, “we should find these sequences to enable more specific vaccines,” Dr. Maedler said.

SOURCE: https://bit.ly/3k1H3fi Cell Reports Medicine, online August 17, 2021.

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