Subscribe
 
 

Deciphering Dengue

12 March 2002 (All day)
Comments

Innards unveiled. Scientists have decoded the 3D structure of dengue.

Researchers have deduced the structure of the dengue virus, which causes mosquito-borne diseases that sicken 50 million people and kill 25,000 each year. The work defines a new type of virus structure, and it could spur the development of drugs and vaccines to stop dengue fever and related mosquito- and tick-borne diseases.

Dengue fever is endemic in many tropical and subtropical regions, but no treatments or vaccines are available. Some patients develop dengue hemorrhagic fever, which causes an enlarged liver, high fever, bleeding from the nose, mouth, and gums, and sometimes death. Virologist Richard Kuhn and structural biologist Michael Rossman of Purdue University in West Lafayette, Indiana, and their colleagues sought to decipher the virus' structure, in the hope that it might provide a way to stop the virus from infecting cells.

The team grew a weakened strain of dengue in vats of cultured mosquito cells, froze the samples, and examined the virus particles under an electron microscope. After recording the images of 526 particles in various orientations, they reconstructed a fuzzy image of an individual particle. Using other researchers' data on the 3D structure of a protein coating from a closely related virus, they wrote a computer program to sharpen that image.

The result--the first complete structure of a virus in the flavivirus family--reveals a layered, soccer-ball-like shape lacking the spiky projections characteristic of many human viruses, the researchers report in the 8 March issue of Cell. Like other viruses, the viral genome is packed in protein and surrounded by a lipid membrane. But unconventionally, that, in turn, is tightly encased in 90 copies of armorlike coat protein. The Purdue lab was surprised that the armor fit so snugly, making it apparently more difficult for dengue to infect cells. But the virus jumps that hurdle, says Rossman: After cells swallow the virus and trap it in lipid vesicles, the virus expands to break its armor, which allows the virus membrane to meld with the lipid vesicles, freeing the virus to reproduce.

The crucial insight is how the coat protein assembles to form the virus' tight armor, says structural virologist Félix Rey of Centre National de la Research Scientique in Gif-Sur-Yvette, France. "It's a major contribution." That knowledge, combined with earlier research by Rey and others, could hint at novel ways to block the virus from infecting cells, says virologist John Roehrig of the Centers for Disease Control and Prevention's Division of Vector-Borne Diseases in Fort Collins, Colorado.

Related sites
WHO fact sheet on dengue
Controlling the spread of dengue
CDC information on dengue

Posted In: