August 18, 2005
Researchers Discover Model Organism For Studying Viruses that Affect Humans
RIVERSIDE, Calif. "“ Researchers at the University of California, Riverside have discovered that a simple worm, called C. elegans, makes an excellent experimental host for studying some of the most virulent viruses that infect humans.
The researchers published their findings in the Aug. 18 issue of the journal Nature in a paper titled, Animal virus replication and RNAi-mediated antiviral silencing in C. elegans.UCR Professor of Plant Pathology Shou-Wei Ding co-authored the paper with Morris Maduro, assistant professor of biology; Feng Li, a graduate student in microbiology; Rui Lu and Hongwei Li, postdoctoral researchers in Ding's laboratory; and research specialists Gina Broitman-Maduro and Wan-Xiang Li. Lu and Maduro are co-first authors of this Nature paper. The National Institutes of Health and the U.S. Department of Agriculture supported the research.
The paper reflects a major step forward in the study of how some of the world's most virulent viruses, such as West Nile, SARS, Ebola and Hepatitis C interact with their hosts.
"All these viruses are very dangerous and are traditionally studied in animal models, so large-scale genetic studies of the host-virus interaction is very hard to do," said Ding, who works in the Center for Plant Cell Biology at UCR's Institute for Integrative Genome Biology. "Needless to say, we are all very excited to find that this little worm can be used to understand how hosts genetically control viruses."
For years researchers throughout the world have studied C. elegans because many aspects of its biology, such as genetics, development and the workings of neurons, mirror the biology of humans. However, no viruses were known to infect the millimeter-long roundworm so it was not used as a model for studying viral infections.
The Nature paper now shows that UC Riverside researchers have developed a strain of the worm, C. elegans, in which an animal virus could replicate, allowing them to map the delicate dance of action and reaction between virus and host.
The UCR team has shown that virus replication in the worm triggers an antiviral response known as RNA silencing or RNA interference (RNAi). RNAi specifically breaks down the virus' RNA. Virus RNA creates proteins that allow the virus to function. The virus responds by producing a protein acting as a suppressor of RNAi to shut down the host's antiviral response. Virus infection did not occur when the viral RNAi suppressor was made inactive by genetic mutations in the host system.
C. elegans' RNAi system is considered a "blanket system," meaning that it has parallels in humans, making the worm model discovered by Ding and his colleagues a valuable tool in studying the way viruses interact with hosts. This tool may speed the discovery of treatments for virus-caused diseases that plague humans.
"The RNAi machinery is very similar between humans and C. elegans, and human viruses such as Influenza A virus and HIV are known to produce RNAi suppressors," Ding said. "So now, the question is can we treat human viral diseases using chemical inhibitors of viral RNAi suppressors?"
The methods outlined in the Nature paper are now being used to generate additional C. elegans strains for screening chemical compounds that inactivate RNAi suppressors associated with avian flu, HIV and others.
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