Epstein-Barr Virus Protein Crucial To Its Role
In Blood Cancers
(Philadelphia, PA) - Researchers at the University of Pennsylvania
School of Medicine have identified a link between a critical
cancer pathway and an Epstein-Barr Virus (EBV) protein known to be expressed
in a number of EBV-associated cancers. Their findings demonstrate a new
mechanism by which EBV transforms human B cells from the immune system
into cancerous cells, which can lead to development of B-cell lymphomas.
Erle S. Robertson, PhD, Associate Professor of Microbiology
and Director of Tumor Virology, with Penn’s Abramson Cancer
Center and MD/PhD student Jason Knight, published
their results in the early March issue of Molecular and Cellular Biology.
Using human cell cultures infected with the Epstein-Barr virus, the investigators
found that a specific viral protein targets a molecule that normally regulates
the cell-cycle progression, or duplication process, of resting B cells.
In the presence of this viral protein - called EBNA3C (for EBV nuclear
antigen) - the cell cycle of the usually quiescent human B cells gets
a jump start, which ultimately initiates uncontrolled growth.
EBV, a member of the herpesvirus family and one of the most common human
viruses, plays a role in cancers such as lymphoproliferative diseases
in transplant or AIDS patients, Burkitt’s lymphoma, Hodgkin’s
lymphoma, and nasopharyngeal carcinoma, and also causes the well-known
disease, infectious mononucleosis. As many as 95 percent of adults 20
years and older have been infected with EBV, but show no symptoms.
“Viruses that are associated with cancers typically target the cell
cycle to gain control,” says Robertson. “However, this is
the first time that laboratory research into how EBV drives the cancer
process has directly identified a critical component of the cell cycle
for control. Now we can develop targeted therapeutics to disrupt the function
of this viral protein.” The researchers surmise that the first use
of future therapies from these studies will be in lymphoproliferative
disease in transplant and immunocompromised patients because this is a
clear case of EBV-driven B-cell lymphoma.
The use of peptides to block the interaction between this essential EBV
protein and the specific pathway in human B cells is currently underway.
Initial studies show that the growth of EBV-associated cancer cells can
be inhibited in tissue-culture assays. The investigators are actively
pursuing this line of investigation for developing potential therapies.
This research was funded by the National Institutes of Health and the
Leukemia and Lymophoma Society of America. Nikhil Sharma, a student from
Cherokee High School, New Jersey who volunteers at Penn, was also a co-investigator
in this study.
The Abramson Cancer Center of the University of Pennsylvania
was established in 1973 as a center of excellence in cancer research,
patient care, education and outreach. Today, the Abramson Cancer Center
ranks as one of the nation’s best in cancer care, according to U.S.
News & World Report, and is one of the top five in National Cancer
Institute (NCI) funding. It is one of only 39 NCI-designated comprehensive
cancer centers in the United States. Home to one of the largest clinical
and research programs in the world, the Abramson Cancer Center of the
University of Pennsylvania has 275 active cancer researchers and 250 Penn
physicians involved in cancer prevention, diagnosis and treatment.
PENN Medicine is a $2.7 billion enterprise dedicated
to the related missions of medical education, biomedical research, and
high-quality patient care. PENN Medicine consists of the University of
Pennsylvania School of Medicine (founded in 1765 as the nation's first
medical school) and the University of Pennsylvania Health System.
Penn’s School of Medicine is ranked #3 in the nation for receipt
of NIH research funds; and ranked #4 in the nation in U.S. News &
World Report’s most recent ranking of top research-oriented medical
schools. Supporting 1,400 fulltime faculty and 700 students, the School
of Medicine is recognized worldwide for its superior education and training
of the next generation of physician-scientists and leaders of academic
Penn Health System is comprised of: its flagship hospital, the Hospital
of the University of Pennsylvania, consistently rated one of the nation’s
“Honor Roll” hospitals by U.S. News & World Report; Pennsylvania
Hospital, the nation's first hospital; Presbyterian Medical Center; a
faculty practice plan; a primary-care provider network; two multispecialty
satellite facilities; and home health care and hospice.