Researchers at The Wistar Institute, Pennsylvania, have identified a new potential pathway for developing therapeutic agents that target Epstein-Barr virus (EBV), according to Science Daily.
The Wistar Institute is an independent, nonprofit research institution in biomedical science, with special expertise in oncology, immunology, infectious disease and vaccine research.
The researchers found that the way the EBV genome folds and expresses itself is more complex than originally thought. They discovered therapeutic molecules that could be targeted to disrupt this genome folding.
Corresponding author Dr. Italo Tempera of The Wistar Institute said, “We identified two cellular proteins that are important to folding the EBV genome.”
“There are existing drugs that target one of these proteins. And our data suggests that if we use that drug on EBV infected cells, we have a way in which we can actually interfere with the folding,” he added. “That means we can interfere in the way in which the EBV viral genome is functioning.”
Worldwide, EBV affects over 90% of individuals. It has the ability to change its gene expression. When viral genes are expressed, the virus infects B-cells (a type of white blood cell of the lymphocyte subtype). This causes the cells to over-multiply, especially in immunocompromised people.
Dr. Tempera and his team wanted to understand the mechanics behind how the virus manipulates its genetic expression.
He said, “The virus was clever to use the same machinery that regulates the conformation of the human genome to also regulate its own gene expression.”:
The researchers found that EBV uses two proteins – CTFC and PARP1 – that play a key role in expressing the human genome.
Olaparib, sold under the brand name Lynparza, is a PARP inhibitor, which is used for the treatment of BRCA-mutated advanced ovarian cancer in adults. The researchers suggest that olaparib may also help treat EBV-positive lymphomas.
Dr. Tempera said, “Usually PARP1 is targeted in the context of DNA damage.”
“Our paper shows that there is another role of PARP1 in the chromatin folding, so this suggests that maybe we can expand the way in which we can use this drug not only to interfere with DNA damage,” he added. “but we also might interfere with DNA folding and gene expression, which is something that we are testing now in the lab.”
Recently, a new study has confirmed that the EBV triggers multiple sclerosis (MS), suggesting that a vaccine against EBV could significantly reduce the incidence of MS. The study, published in the journal Science, was conducted on 10 million US military personnel, which showed that virtually EBV precedes every case of MS.
