Every year, about 390 million people are infected with dengue virus, which is primarily spread by Aedes mosquitoes, with tropical climates hit hardest.
Because there is no treatment or vaccine for dengue, the main method of controlling the disease has focused on reducing mosquito breeding sites and supportive care, such as fluid replacement, for patients with severe dengue.
Now, researchers have identified a protein secreted by cells infected with the mosquito-borne dengue virus. Called nonstructural protein 1 (NS1), it is the only one of the 10 viral proteins secreted by infected cells to circulate freely in the bloodstream.
In experiments conducted on human lung endothelial cells and in mice, the researchers showed that NS1 caused permeability of the endothelium, which lines the walls of blood and lymph vessels. They found that the protein itself, separate from the dengue virus, can cause blood vessels to leak fluid.
NS1 is produced by all serotypes of dengue virus. The researchers homed in on this viral protein after they noticed that the pathogenic effects of dengue virus infection were blocked in mice that had generated antibodies to NS1.
The team found that mice injected with NS1 alone, without the virus present, developed symptoms of dengue disease that included a cascade of inflammatory cytokines, vascular leakage and fluid loss. If the researchers added a sublethal dose of dengue virus type 2, the resulting infection was fatal.
On the other hand, immunization of mice with recombinant NS1 from each of the four serotypes protected mice against vascular leak and the lethal effects of dengue virus type 2.