For immediate release: December 2, 2002
Contact: Steven Schultz (609) 258-5729, email@example.com
Caught sleeping: Study captures virus dormant in human cells
Cytomegalovirus, hidden in most people, begins
to give up secrets of its stealth
PRINCETON, N.J. -- Princeton scientists have taken an important
step toward understanding a virus that infects and lies dormant in
most people, but emerges as a serious illness in transplant patients,
some newborns and other people with weakened immune systems.
The virus, called human cytomegalovirus, enters the bone marrow
and can hide there for a lifetime. Until now, however, scientists
had not been able to study the virus in its latent stage because it
infects only humans and does not readily infect or become dormant
in laboratory strains of bone marrow cells.
In a study published online Nov. 27, Felicia Goodrum, a postdoctoral
fellow, and Tom
Shenk, a professor of molecular biology, demonstrated a laboratory
system for studying the virus in its latent stage. They showed they
could establish a latent infection in freshly collected bone marrow
cells and then retrigger an active infection. They drew on their system
to discover a set of genes that the virus uses in its latent state
and that may give the virus its great capacity for stealth.
Knowing what genes the virus uses to hide and re-emerge could give
pharmaceutical companies targets for designing drugs that disrupt
those mechanisms. "So you could dream that some day in the future
we could clear the virus from a person and not just treat the symptoms
that occur when the virus re-emerges," said Shenk.
Cytomegalovirus is in a broad family of herpes-related viruses,
which includes the virus that causes chicken pox and shingles. The
only treatment doctors currently have for cytomegalovirus is an antiviral
drug called gancyclovir, which stops the virus from replicating during
its active infection phase, but has no effect during the latent stage,
when the virus does not replicate.
Another possible use for the research would be to develop a diagnostic
test that indicates when the virus is likely to reactivate itself.
If scientists could pinpoint genes that turn on just in advance of
reactivation, then doctors could use that information in deciding
whether to administer antiviral drugs to their patients. Currently,
doctors prescribe gancyclovir preemptively for many patients, even
though it has significant side effects.
The researchers described their results in an online edition of
the Proceedings of the National Academy of Sciences. It is scheduled
to appear in the journal's Dec. 10 print edition. Goodrum and Shenk
collaborated with Craig Jordan of the University of Kentucky Medical
Center and Kevin High of the Wake Forest University School of Medicine,
who supplied human bone marrow cells and expertise in working with
The key to the study's success, said Shenk, was Goodrum's painstaking
work in learning to handle freshly harvested bone marrow cells in
the lab and to maintain them in a state that matches as closely as
possible their condition in the human body. Her supply of cells was
limited because they are badly needed for bone marrow transplantations.
Goodrum could use only cells that were caught in a filter used in
Shenk said her work makes it possible to answer big questions that
have long eluded researchers. It is unknown, for example, what specific
cells the virus infects among the many constituents of bone marrow.
In their study, Goodrum narrowed the search to a group of cells that
constitute just 1 percent of bone marrow cells. The next step, said
Goodrum, will be to look at even smaller subpopulations of cells and
compare the activity of the virus and its genes in each of them.
"We'd like to know the answers to some very basic questions,"
said Goodrum. "How many copies of the virus are there in an infected
cell? And how exactly do they get passed along?"
"These are all things you get to think about when you have a
model system," said Shenk. "You couldn't do it without the
system Felicia developed."
Understanding the virus is important because roughly half of all
organ or bone marrow transplant patients, who are always given immune-suppressing
drugs, experience some complication with cytomegalovirus, said Shenk.
Women who become infected or experience a reactivation during a pregnancy
risk passing the virus to the fetus, which can lead to birth defects,
including deafness and developmental disorders.
Between 50 and 85 percent of Americans become infected with cytomegalovirus
by age 40, according to the National Institutes of Health. Shenk said
he believes the figure may be even higher, because every sample Goodrum
has studied had at least some cells that were infected with the virus.