Researchers led by Janet Smith of the University of Michigan Life Sciences Institute describe for the first time the structure of a protein that helps the viruses replicate and spread infection.

"Seeing the design of this key protein provides a target for a potential vaccine or even a therapeutic drug," Smith said.

The protein, NS1, is produced inside infected cells, where it plays a key role in replication of the virus.
NS1 is also released into the bloodstream, where it may help disguise the infection from the patient's immune system and may play a role in the hemorrhage that is seen in severe dengue virus infection.
"Having the structure of NS1 is a huge advance in understanding, and using, the protein to our advantage," said Richard Kuhn, who led the Purdue University team involved in the work.

"Understanding how the protein is designed provides an easier pathway to understanding its roles in the virus life cycle. We now know which portions of the protein to target in drug development to shut it down and stop the progression of infection," said Kuhn.
The researchers discovered that NS1 has a 3-D structure with two distinct sides, one facing the replication system of the virus inside cells it infects and the other facing the immune system outside infected cells.
"The two faces of NS1 define the regions responsible for its two major functions," Smith said.
"This understanding will guide future research into dissecting and targeting these regions in disease treatment or prevention," Smith said.
Developing a clearer picture of how the NS1 protein interacts with the immune system and influences disease may pave the way for researchers to develop a vaccine that protects people - without inadvertently increasing their risk.
The study was published in the journal Science.


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