Scientists identify therapeutic target for Epstein-Barr virus

Date:
January 18, 2022
Source:
The Wistar Institute
Summary:
A new study has identified a new potential pathway for developing
therapeutics that target Epstein-Barr virus (EBV).



FULL STORY ==========================================================================
A new study by researchers at The Wistar Institute, an international
biomedical research leader in cancer, immunology, infectious disease, and vaccine development, has identified a new potential pathway for developing therapeutics that target Epstein-Barr virus (EBV). They discovered that
the way the EBV genome folds, and thereby expresses itself and causes
disease, is more complex than researchers originally thought, and they identified molecules that could be targeted to disrupt this folding.


==========================================================================
"We identified two cellular proteins that are important to folding
the EBV genome." said Italo Tempera, Ph.D., associate professor in
the Gene Expression & Regulation Program at The Wistar Institute and corresponding author on the paper. "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. That means we can interfere in the way in which the
EBV viral genome is functioning." EBV, which affects more than 90%
of individuals worldwide, is a dynamic virus, meaning that it can
change its gene expression. If certain viral genes are expressed,
the virus infects B-cells and causes them to overmultiply, which is
especially problematic in individuals with suppressed immune systems,
such as transplant patients.

Tempera and his colleagues wanted to understand the mechanics behind how
the virus manipulates its genetic expression. To do this, they used a
modified DNA sequencing technique to examine how the genome folds under different conditions.

"The virus was clever to use the same machinery that regulates
the conformation of the human genome to also regulate its own gene
expression," said Tempera.

Specifically, the researchers found that EBV uses two proteins, CTFC
and PARP1, that also play a role in the expression of the human genome.

PARP1 is already a target of the drug, olaparib (sold under the brand
name Lynparza), which is used to treat patients with ovarian cancer. This
new study suggests that the drug may have a use for treating EBV positive lymphomas, as well.

"Usually PARP1 is targeted in the context of DNA damage," said
Tempera. "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,
but we also might interfere with DNA folding and gene expression,
which is something that we are testing now in the lab." Co-authors:
Sarah M. Morgan, Lisa Beatrice Caruso, Andrew Kossenkov, Sarah Boyle,
Paul M. Lieberman, and Italo Tempera from The Wistar Institute; Hideki
Tanizawa from University of Oregon; Michael Hulse from Fels Institute
for Cancer Research and Molecular Biology, Lewis Katz School of Medicine
at Temple University; Jozef Madzo and Kelsey Keith from The Coriell
Institute for Medical Research; Yinfei Tan from Fox Chase Cancer Center.

========================================================================== Story Source: Materials provided by The_Wistar_Institute. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Sarah M. Morgan, Hideki Tanizawa, Lisa Beatrice Caruso, Michael
Hulse,
Andrew Kossenkov, Jozef Madzo, Kelsey Keith, Yinfei Tan, Sarah
Boyle, Paul M. Lieberman, Italo Tempera. The three-dimensional
structure of Epstein-Barr virus genome varies by latency type and
is regulated by PARP1 enzymatic activity. Nature Communications,
2022; 13 (1) DOI: 10.1038/s41467-021-27894-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220118104136.htm

--- up 6 weeks, 3 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)