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UI researchers publish findings on dengue virus
IOWA CITY, Iowa -- University of Iowa researchers now know more about the
virus that causes dengue fever, a mosquito-borne illness that affects as many
as 50 million people worldwide each year.
In an article in the August issue of Nature Medicine, UI researchers, along
with scientists at the University of Michigan, the University of California-San
Diego and the University of Otago in Dunedin, New Zealand, describe how the
dengue (pronounced DEN-ghee) virus binds to human cells. Moreover, the researchers
report that suramin -- a drug used to treat parasitic infections and some
forms of cancer -- prevents this binding from occurring.
"This is not a cure, but it's an important step toward developing a
potential treatment or vaccine," says Dr. Robert Linhardt, professor
of medicinal and natural products chemistry at the UI College of Pharmacy,
who led the UI team involved in the study. "Dengue virus is a hot subject
right now. There has been a recent outbreak in Cuba and dengue remains a major
health risk in Africa, South America, Central America and even some southern
areas of the U.S."
The dengue virus, most prevalent in Third World tropical regions but also
in subtropical developed countries, causes dengue fever, a severe, flu-like
illness. Symptoms include pain to the joints and muscles, headaches, sore
throat, fever, running of the eyes and an irritating rash. There is no cure,
but recovery usually occurs within several days. Dengue hemorrhagic fever,
a potentially deadlier form of the illness, can cause internal bleeding, circulatory
failure, coma and shock.
"The ebola virus is another type of hemorrhagic fever," Linhardt
says. "Dengue fever can be just as devastating. It's among the worst
diseases out there."
Researchers knew from earlier studies that the dengue virus binds to specific
molecules in the cells targeted for infection. Linhardt and his colleagues
discovered that these molecules are complex sugars known as heparan sulfates,
which are found on the surfaces of the target cells and are present in a variety
of human tissues.
"These heparan sulfate molecules are present in the liver, which suggests
the liver might be one of the initial sites for dengue infection," Linhardt
says. "It's possible that the virus targets to specific tissues in the
body based on the types of receptors in those tissues."
The researchers also showed that suramin, a well-established drug that mimics
the structure of heparan sulfate, prevented the dengue virus from binding
to the target cells, thus inhibiting the infection.
Linhardt notes that molecular modeling done at the UI by colleagues Ronald
Hileman, a postdoctoral associate, and Jonathan Fromm, a student in the M.D./Ph.D.
Medical Scientist Training Program, enabled the researchers to discover the
site on the virus where it binds to the cell receptors. Without this site,
the virus cannot infect the target cells.
"This gives researchers the potential to make a recombinant form of
the virus that would not infect, but generate antibodies that could be used
to develop a vaccine," Linhardt says. "Vaccines are relatively inexpensive
compared to therapies. Many of the people that are most affected by the dengue
virus live in poor, underdeveloped countries. So this could be a major contribution,