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Researchers probe West Nile virus and Dengue fever

By Anastassios Adamopoulos, Daily Staff Reporter
Published February 10, 2014

In a recently published study, researchers from the University and Purdue University reported new findings that could help better understand and treat of a pair of deadly mosquito-born diseases: West Nile fever and Dengue fever. The report was the first to outline the structure of the NS1 protein responsible for helping the viruses spread.

The research was led by Biological Chemistry Prof. Janet Smith and Richard Kuhn, director of the Bindley Bioscience Center at Purdue University.

“We’ve had it in our sights for about 10 years,” Smith said. “We’ve been working pretty intensively on it, I would say, for five or six years.”

West Nile fever, which was first introduced to North America in 1999, and has since been found in each of the lower 48 states. In 2013, there were 36 reported cases of the disease in Michigan, resulting in two deaths, according to the Centers for Disease Control.

More than 400 million people worldwide are infected by Dengue fever annually, with seven reported cases in Michigan in 2013, according to the CDC and the U.S. Geological Survey. The disease affects most of the countries in the equatorial belt and has reached the southern United States.

Both West Nile and Dengue fever are transmitted to humans via infected mosquitoes and can result in high fever, muscle pain, headaches and vomiting. In certain severe cases, both diseases can be deadly.

The NS1 protein described in the report originates in infected cells, and is responsible for the viruses' development. Once it’s in the bloodstream, it can cause bleeding, and hide the infection from the immune system.

“What we didn’t know before but we know now is which parts of the protein are responsible for helping the virus to get replicated inside cells and which parts of the protein are involved in interactions with the immune system when it gets secreted into the bloodstream,” Smith said.

The structure of the protein was illuminated through a process known as x-ray crystallography, which uses x-ray beams to determine 3-D structure of crystalline solids. The imaging procedure was performed at the Argonne National Laboratory in Illinois, but the difficult process of purifying the protein was performed in Smith’s lab at the University.

“A lot of times in crystallography, when you do this technique, one of the major blocks is to be able to produce enough protein that is uniform, homogeneous” Kuhn said.

There are currently no known effective treatments for these diseases, but the research team said they are hopeful that their findings could lead to the development of vaccines.

“We are planning a whole series of experiments to think about antivirals and think about developing vaccine strategies,” Kuhn said.

NS1 is an unusual protein because it comes out of the infected cell, which makes it a target, Kuhn said. The protein also has various jobs throughout the infection cycle. The right antiviral could potentially attack the protein in multiple steps in the life cycle of a virus and disable it.

Kuhn said he has been in discussions with companies to develop vaccines against Dengue virus. However, finding the right vaccine for Dengue virus is a complicated process, since there are four different strains of the virus. Scientists are still working to better understand the interactions between these forms of the disease.

“People get the most severe forms of the disease, it seems, when they’ve been infected by more than one of the four types,” Kuhn said.

In the future, Smith said she wants to explore if NS1 is related to this differentiation, which is an important factor in the creation of a vaccine that could target a specific form of the disease with minimal complications.

Smith will give a lecture on crystallography on Feb. 20 at 4 p.m. at Palmer Commons.


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