Inhibiting a specific metabolic pathway may reduce latent Epstein-Barr virus infection.
Most people are carriers of EBV: 90% of the adult population are infected with the virus and usually have no symptoms or associated illness.. About 50% become infected before the age of five, but many people do not become infected until they are teenagers. Acute infection with the virus can cause glandular fever, also known as “kissing disease”, and can render infected people unconscious for several months. In addition to its carcinogenic properties, the pathogen is also suspected of being involved in the development of autoimmune diseases such as multiple sclerosis. Currently, no approved drug or vaccine can specifically target EBV in the body. Now a research team from the University of Basel and University Hospital Basel has reported a promising starting point for the fight against EBV. Researchers led by Professor Christoph Hess deciphered how immune cells infected with EBV are reprogrammed, so-called B cells. This process, known as “transformation”, is necessary for the infection to become chronic and cause subsequent diseases such as cancer. Specifically, the team found that the virus causes the infected cell to increase production of an enzyme known as IDO1. This ultimately leads to increased energy production by the infected cells’ powerhouses: the mitochondria. In turn, this additional energy is necessary for increased metabolism and rapid proliferation of B cells thus reprogrammed by EBV.
Research results
Clinically, the researchers focused on a group of patients who developed blood cancer caused by EBV after organ transplantation. For prevent transplanted organ rejection, it is necessary to weaken the immune system with the help of medications. This, in turn, allows EBV to take over and cause a blood cancer known as post-transplant lymphoma. In a paper now being published, the researchers were able to show that EBV activates the enzyme IDO1 months before post-transplant lymphoma is diagnosed. This discovery could help develop biomarkers for the disease. ‘Previously, IDO1 inhibitors were developed in the hope that they could help treat established cancers., which, unfortunately, turned out not to be the case. That is, there are already clinically tested inhibitors of this enzyme,” explains Christoph Hess. Consequently, this class of drugs may now get a second chance in applications aimed at containing EBV infection and therefore treating EBV-related diseases. In fact, in mouse experiments, inhibiting IDO1 with these drugs reduced B cell transformation and therefore reduced B cell transformation. , viral load and lymphoma development. “In transplant patients, it is common practice to use drugs against various viruses. “There is nothing specific yet for the prevention or treatment of diseases associated with the Epstein-Barr virus,” Hess concludes.