SEATTLE - Researchers at the Fred Hutchinson Cancer Research Center and the
University of Washington have discovered a mechanism that may open a new window of understanding into the process of how retroviruses such as HIV infect cells.
A report of this discovery, by senior author Julie Overbaugh, Ph.D., and
colleagues, will appear tomorrow in Science. The paper sheds new light on how the feline leukemia virus, or FeLV, infiltrates cells. This retrovirus can cause a deadly form of immune deficiency in cats that can also increase cancer risk.
In retroviral infection, a virus infects a new host through receptor proteins on cells
at the infection site, much like a key fits into a lock. Once an individual is infected, the virus gains foothold by undergoing a series of genetic mutations designed to invade new sets of receptors, allowing it to continually evade detection, attack, and ultimately shut down the body's defenses. This shutdown occurs when mutated versions of the virus infect and destroy the body's T cells, which are critical to immune function.
Now, scientists studying FeLV have identified another factor in the infection
process: a secondary retroviral receptor (or cofactor) that is crucial for the mutated, or T-cell adapted, virus to do its work. Without this receptor, appropriately dubbed FELIX, the virus would be unable to set up shop.
"It was a surprising and unique finding," says Overbaugh, a member of the
Hutchinson Center's Human Biology and Public Health Sciences divisions and an affiliate professor of microbiology at the University of Washington.
"This discovery redefines how retroviruses can infect cells," she says. "We don't
really understand exactly how the initial infection process works, but bringing in this other component may provide a window into the pathway."
The next step for researchers is to determine whether the presence of this cellular
cofactor, a prerequisite to FeLV infection, extends to human retroviruses such as HIV.
"If a FELIX-type activity also can be found in humans, the question is whether
one could create a therapy that would disable it and thus disarm the virus," Overbaugh says.
From a biological standpoint, FELIX also is unique. Instead of being buried in the cell's membrane, which is were most receptors are located, it is actually a protein that is secreted to the exterior of the cell.
"We were looking for this receptor for 10 years, and we couldn't crack it,"
Overbaugh says. "When we finally found it, at first we thought we couldn't be right, because there was no precedent for a secreted receptor."
This work was funded by the National Cancer Institute.
Editor's note: To arrange an interview with Dr. Overbaugh, please contact
Kristen Woodward, (206) 667-5095. For a copy of the Science article, contact the journal at (202) 326-6440 and ask for article No. 19, or e-mail firstname.lastname@example.org.
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The Fred Hutchinson Cancer Research Center is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Recognized internationally for its pioneering work in bone-marrow transplantation, the Center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. The Hutchinson Center is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest. For more information, visit the Center's Web site at <www.fhcrc.org>.
CONTACT: Kristen Woodward
FOR IMMEDIATE RELEASE
March 9, 2000