The University Record, September 3, 1997

Research team gains insights into dengue fever

By David Wilkins
Medical Center Public Relations

Researchers have a new understanding of the way dengue virus binds to human cells--and how to stop it from doing so.

The mosquito-borne dengue virus causes dengue fever, a severe flu-like illness the World Health Organization (WHO) calls "the most important and rapidly increasing arbovirus in the world."

The disease is prevalent in Third World tropical regions and is spreading to subtropical developed countries, including the United States. WHO estimates that 50 million cases of dengue fever occur worldwide each year, including a potentially deadly form of the disease called dengue hemorrhagic fever.

Most cases occur in children.

A team of researchers from the University of Michigan and the University of Iowa have gained new insights into the way the virus attacks at a cellular level. Their findings were published in the August issue of Nature Medicine.

"Dengue is a very significant world public health problem which has largely been ignored in the developed world," says Rory Marks, assistant professor of internal medicine. "There's no specific treatment for infection and no way to prevent progression to the more deadly forms of the disease. No vaccine is available or likely to become available any time soon.

"Programs to control dengue infection have focused on killing the mosquito responsible for transmitting the virus to humans," Marks says. "These measures were very effective in the past but appear to have failed in recent years. The mosquitoes appear to be winning this latest war."

New approaches for the control of dengue virus infection--specifically aimed at aspects of dengue virus infectivity other than mosquito control--are urgently needed, Marks says.

The research team has discovered the mechanism the virus uses to attach itself to cells it will infect--and they can block it from doing so in laboratory tests. "It provides something to work from to develop a potential treatment," Marks says.

Marks points out that dengue fever is:

 

An enormous social and economic burden throughout much of the developing world.

 

Spreading to the developed world, including frequent epidemics within U.S. territory, in Puerto Rico.

 

Increasingly prevalent after the withdrawal of mosquito control programs. "It is controversial whether wealthy nations, particularly the United States, have a continuing responsibility for controlling diseases that mainly threaten developing countries," Marks says.

In earlier studies, the researchers concluded that a particular dengue virus protein--called the envelope protein--is responsible for binding the virus to cells targeted for infection. Their latest work takes that a step further by showing that dengue infection occurs when the virus binds to a type of sugar molecule they identified as heparan sulfate, which is found on the surface of the target cell.

Marks and his colleagues also prevented that binding from occurring--and inhibited the infection--through the use of a drug called Suramin, chosen because it mimics the structure of heparan sulfate. It's questionable whether Suramin ultimately will be u sed to treat dengue infections, Marks said. This, however, is the first demonstration that a drug can effectively prevent infection by dengue virus, and it provides a basis for screening related compounds that may inhibit the virus safely and effectively.

Dengue virus is one of a large family of viruses, called flaviviruses, many of which cause serious human diseases. These include yellow fever and hepatitis C viruses. Most flaviviruses have similar envelope proteins, and it is expected that they share the same basic mechanism for binding to cells. "We expect our work with dengue virus to also hold true for these other viruses," Marks said.