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"We discovered two cellular proteins that are important for folding the EBV genome," said Dr.
Italo Tempera from the Wistar Institute
.
"Drugs are currently available that target one of these proteins
EBV is a dynamic virus, meaning it can change its own gene expression, and it affects more than 90 percent of people worldwide
.
If certain viral genes are expressed, the virus can infect B cells, causing them to overproduce, which is especially problematic for people with suppressed immune systems, such as transplant patients
Tampara and his colleagues wanted to understand the mechanisms behind how viruses manipulate their gene expression
.
To do this, they used a modified DNA sequencing technique to study how the genome folds under different conditions
"This virus is smart and uses the same mechanisms that regulate the conformation of the human genome to regulate its own gene expression," said Tempera
.
Specifically, the researchers found that EBV uses two proteins, CTFC and PARP1, which are also in humans the expression of the genome
PARP1 is already a target of olaparib (brand name Lynparza) for ovarian cancer
.
The new study suggests that the drug may also be useful in the treatment of EBV-positive lymphomas
"Normally, PARP1 is the target of DNA damage," Tampara said
.
"Our paper shows that there is another role for PARP1 in chromatin folding, suggesting that maybe we can expand the way we can use this drug to not only interfere with DNA damage, but we might also interfere with DNA folding and gene expression, which It's what we're testing in the lab right now
Co-authors: Sarah M.
Journal Reference :
Sarah M.
