The Epstein-Barr virus (EBV) can cause a range of diseases, including cancers. However, no drug or approved vaccination can specifically thwart EBV within the body. Now, new research shows that inhibition of a specific metabolic pathway in infected cells can diminish latent infection and the risk of downstream disease.
The findings are published in Science in an article titled, “A metabolic dependency of EBV can be targeted to hinder B cell transformation.”
Researchers from the University of Basel and the University Hospital Basel led by Christoph Hess, PhD, professor at the University of Basel, have deciphered how the immune cells infected with EBV are reprogrammed. Known as “transformation,” this process is necessary for the infection to become chronic and cause subsequent diseases such as cancer. Specifically, the team discovered that the virus triggers the infected cell to ramp up the production of an enzyme known as IDO1. This ultimately leads to greater energy production by the power plants of infected cells: the mitochondria. In turn, this additional energy is needed for the increased metabolism and the rapid proliferation of B cells reprogrammed by EBV in this way.
Clinically, the researchers focused on a group of patients who had developed EBV-triggered blood cancer following organ transplantation. To prevent a transplanted organ from being rejected, it is necessary to weaken the immune system using medications. This, in turn, makes it easier for EBV to gain the upper hand and causes blood cancer, referred to as post-transplant lymphoma.
The researchers were able to show that EBV upregulates the enzyme IDO1 months before post-transplant lymphoma is diagnosed. This finding may help to develop biomarkers for the disease.
“Previously, IDO1 inhibitors have been developed in the hope that they could help to treat established cancer—which has unfortunately turned out not to be the case. In other words, there are already clinically tested inhibitors against this enzyme,” explained Christoph Hess. Accordingly, this class of drugs might now receive a second chance in applications aimed at dampening EBV infection and thereby tackling EBV-associated diseases. Indeed, in experiments with mice, IDO1 inhibition with these drugs reduced the transformation of B cells and therefore the viral load and the development of lymphoma.
“In transplant patients, it’s standard practice to use drugs against various viruses. Until now, there’s been nothing specific for preventing or treating Epstein-Barr virus associated disease,” said Hess.
The new findings provide a promising start to putting the brakes on EBV and may lead to novel treatments for diseases caused by EBV.
