CONTACT: JENNIFER BROWN
Iowa City IA 52242
(319) 335-9917; fax(319) 384-4638
Release: Sept. 20, 2002
UI study reveals how a virus escapes from host cells and returns to the
Your co-worker has a cold. You know it is only a matter of time before the
virus spreads to you and other colleagues, causing a spate of missed workdays.
The ability to spread from person to person makes viral infections, even those
as benign as the common cold, a large public health problem.
Scientists have some understanding of how viruses enter cells and reproduce
once inside. However, much less is known about how the newly generated viruses
exit from the tissue and return to the outside world to infect new hosts.
Now, University of Iowa researchers and colleagues have uncovered a strategy
used by one particular virus to escape from its host's cells back into the
environment. The findings appear in the Sept. 20 issue of the journal Cell.
Adenovirus, which causes colds and pneumonia, infects the airway epithelial
cells that line the respiratory tract. The virus reproduces, and then escapes
to find a new host. In general, epithelial cells line body surfaces and cavities.
They form a physical barrier between the internal and external world.
A family of proteins called cell adhesion molecules hold the epithelial
cells together, acting like a zipper. When the space between epithelial cells
is "zipped," microorganisms cannot enter or exit from the host.
One key component of this zipper, analogous to the teeth of a zipper, is the
cell adhesion molecule CAR.
The UI study shows that infection of cells with adenovirus caused the epithelia
to become leaky, or "unzipped." Closer inspection showed that viruses
moved through gaps formed between cells to gain access to the environment.
The investigators also described the specific molecular event that produces
the gaps between the epithelial cells.
The newly made adenovirus contains a protein on its surface, called fiber.
When fiber binds to CAR it disrupts cell adhesion by CAR. That is, it "unzips"
"We found that fiber protein alone, even without the rest of the virus,
caused a breakdown of cell-cell adhesion," said Robert Walters, an M.D./
Ph.D. student in the UI Medical Scientist Training Program, and lead author
of the study. "Moreover, when we blocked fiber we prevented virus from
escaping across airway epithelia."
The virus also appears to stack the deck in favor of its escape. In addition
to reproducing itself, the virus makes excess fiber protein and defective
viral particles that are not infectious but that do possess fiber. Thus, when
an infected cell dies and spills it contents, the CAR molecules in the vicinity
are swamped by various forms of the viral protein and relinquish their hold
on neighboring cells. Thus the "zipper" falls apart, leaving a gap
between the cells for the virus to use as an escape route.
Walters noted that it was particularly interesting that adenovirus also
exploits the molecular interaction between fiber and CAR to gain entry into
"These results suggest that adenovirus evolved to use one tool for
two quite different jobs," Walters said.
Previous studies have revealed that several other viruses also commandeer
cell adhesion molecules for entry into host cells, and the UI researchers
speculate that the type of escape route used by adenovirus for exiting a host
or crossing tissue barriers may be widely used by other viruses and also by
"Our study tells us that CAR holds epithelial cells together and that
the viral protein disrupts the interaction and allows the virus to get out,"
Walters said. "In most viral infections, people shed the virus before
they are noticeably sick. So being able to understand how that shedding occurs
might allow us to prevent spread of infection among people in close quarters,
such as in schools or military barracks."
In addition to Walters, the research team also included Paul Freimuth, Ph.D.,
professor of biology at Brookhaven National Laboratory, and UI researchers
Thomas Moninger, research assistant in the Central Microscopy Research Facility;
Ingrid Ganske, summer student in internal medicine; Joseph Zabner, M.D., associate
professor of internal medicine; and Michael Welsh, M.D., the Roy J. Carver
Chair in Internal Medicine and Physiology and Biophysics, and a Howard Hughes
Medical Institute Investigator.
The study was funded by the National Heart Lung and Blood Institute, and
the Cystic Fibrosis Foundation.
University of Iowa Health Care describes the partnership between
the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and
Clinics and the patient care, medical education and research programs and
services they provide. Visit UI Health Care online at www.uihealthcare.com.