Scientists at the University of California, Berkeley School of Public Health have identified a key culprit responsible for the fluid loss and resulting shock that are the hallmark of severe—and potentially fatal—dengue virus infections.
A team of researchers led by molecular virologist Dr. Eva Harris, Berkeley professor in the division of infectious diseases and vaccinology, presented new evidence that a guilty party is 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.
Remarkably, the researchers also found that blocking this protein in mice protected them from the lethal effects of dengue virus infection, an important finding given that an effective vaccine against dengue has remained elusive, partly because there are four serotypes of the virus that cause disease.
“This is a missing piece in the puzzle of the pathogenesis of dengue,” said Dr. Harris, senior author of the study published September in the journal Science Translational Medicine. “The role of NS1 itself had been overlooked in severe forms of dengue disease, but we now know that it is an important player. Our findings show that NS1 could be a prime target for drugs, and that it should be considered in vaccine development.”
The National Institute of Allergy and Infectious Diseases helped support this work.