CHICAGO, Jan. 8 (Xinhua) -- Researchers from the University of California, Berkeley, and the University of Michigan (UM) revealed how an antibody called 2B7 neutralizes one specific protein made by dengue virus called NS1, which is short for "non-structural protein 1" and is key to the dengue virus's ability to both replicate and cause disease.
The researchers had previously demonstrated that the protein itself can cause leaks in the endothelial barrier, even in the absence of infectious viral particles. And in cases of dengue virus infection, the more NS1 found circulating in the host's blood, the more severe the infection is likely to be.
In the latest study, the researchers identified specific regions of the protein that are responsible for damaging the endothelial cells: a so-called wing region that allows the protein to connect to the host cells, and another region that triggers destructive events within the endothelial cells.
By analyzing the precise way that the 2B7 antibody attaches to the protein, they found that the antibody is able to neutralize both of these regions simply by getting in the protein's way. The antibody connects to NS1 in such a way that the wing regions cannot reach the endothelial cells, preventing the protein from latching onto the endothelial cells.
"This collaborative approach gives us a lot of great insight into understanding the biology of this protein, its interactions with cells and its pathogenesis," said David Akey, a researcher at the UM Life Sciences Institute and a lead author of the study. "It's an example of combining structure and function to open therapeutic avenues."
By binding only to the NS1 protein and not to the virus particle itself, however, the 2B7 antibody does not lead to antibody-dependent enhancement of the infection.
"These findings tell us that we can really have an effect on the virus's pathogenesis by blocking these sites on just the circulating proteins," said Janet Smith, a professor at the UM Life Sciences Institute and UM Medical School. "It offers a strategy not only for a therapy to treat an infection, but also for a vaccine to prevent infection."
And because the NS1 protein is produced by many flaviviruses, the researchers believe the antibody that targets NS1 may be useful in treating or preventing multiple flaviviruses.
Dengue virus, a member of a group of viruses called flaviviruses, causes 50 to 100 million cases of dengue disease each year, with no effective treatment or vaccine. Other members of this group include the viruses that cause Zika, yellow fever and West Nile fever.
The study was published Friday in the journal Science. Enditem
