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Purdue University is leading a team of researchers in a federally funded effort aimed ultimately at developing better vaccines and antiviral drugs against two types of disease-causing viruses by learning critical details about their life cycles.
The viruses also pose a potential homeland security threat because they have been used to make biological weapons, said Richard Kuhn, a professor and head of the Department of Biological Sciences at Purdue.
“Viruses within these two groups pose significant risks to large segments of the population, and methods for controlling infection and disease are few,” he said. “These are really important human diseases.” One group, called flaviviruses, includes West Nile and dengue. The other group, called alphaviruses, includes eastern equine encephalitis and chikungunya.
“Dengue infects more than 50 million people annually, killing about 24,000 each year, primarily in tropical regions,” Kuhn said.
Both types of viruses are transmitted by mosquitoes and sometimes ticks.
“Although these viruses are now mostly restricted to the tropics, as population density increases in cities and there is a greater global movement of people, there is the fear that these viruses are going to gain a greater geographical range,” Kuhn said. “There also is the possibility of terrorists using weapons made from these viruses, so a better understanding of their life cycles could lead to ways to defend against attacks.”
The work is funded with a two-year $4 million American Recovery and Reinvestment Act grant through the National Institutes of Health’s National Institute of Allergy and Infectious Diseases.
The researchers will use advanced imaging technologies, including cryoelectron microscopy and X-ray crystallography, along with techniques in biochemistry, molecular biology, and genetics, to uncover critical structural details about the viruses.
Both types of viruses have a two-layer outer protein-and-lipid membrane envelope and a genome of RNA, or ribonucleic acid. In alphaviruses, the heads of key proteins protrude outward like spikes, with the tails extending into the virus. The proteins in the flaviviruses lie flat on the surface of the virus’ outer shell, which resembles a golf ball’s bumpy shape.
“The current understanding of alphavirus and flavivirus life cycles at the molecular level is incomplete because we lack a structural foundation for the viral and host proteins involved in RNA replication, how this genome is packaged, and how the virus is assembled inside the host cells,” Kuhn said. “We are interested in their life cycles.
“What do they look like? How do they get into cells? What happens once they do? Then, how do they assemble themselves and exit the host cells?”
Researchers also will probe how antibodies bind to the viruses.
“Using structural information, we can figure out how the antibodies work and which sites they specifically bind to on the outside of the viruses, and those findings may lead to better vaccines and antiviral drugs and a better understanding of how the viruses infect host cells,” Kuhn said.
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Source: Purdue University
