Researchers at the University of California, Riverside havediscovered that a simple worm, called C. elegans, makes an excellentexperimental host for studying some of the most virulent viruses thatinfect humans.
The researchers published their findings in theAug. 18 issue of the journal Nature in a paper titled, Animal virusreplication and RNAi-mediated antiviral silencing in C. elegans.
UCRProfessor of Plant Pathology Shou-Wei Ding co-authored the paper withMorris Maduro, assistant professor of biology; Feng Li, a graduatestudent in microbiology; Rui Lu and Hongwei Li, postdoctoralresearchers in Ding’s laboratory; and research specialists GinaBroitman-Maduro and Wan-Xiang Li. Lu and Maduro are co-first authors ofthis Nature paper. The National Institutes of Health and the U.S.Department of Agriculture supported the research.
The paperreflects a major step forward in the study of how some of the world’smost virulent viruses, such as West Nile, SARS, Ebola and Hepatitis Cinteract with their hosts.
“All these viruses are very dangerousand are traditionally studied in animal models, so large-scale geneticstudies 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 forIntegrative Genome Biology. “Needless to say, we are all very excitedto find that this little worm can be used to understand how hostsgenetically control viruses.”
For years researchers throughoutthe world have studied C. elegans because many aspects of its biology,such as genetics, development and the workings of neurons, mirror thebiology of humans. However, no viruses were known to infect themillimeter-long roundworm so it was not used as a model for studyingviral infections.
The Nature paper now shows that UC Riversideresearchers have developed a strain of the worm, C. elegans, in whichan animal virus could replicate, allowing them to map the delicatedance of action and reaction between virus and host.
The UCR teamhas shown that virus replication in the worm triggers an antiviralresponse known as RNA silencing or RNA interference (RNAi). RNAispecifically breaks down the virus’ RNA. Virus RNA creates proteinsthat allow the virus to function. The virus responds by producing aprotein acting as a suppressor of RNAi to shut down the host’santiviral response. Virus infection did not occur when the viral RNAisuppressor was made inactive by genetic mutations in the host system.
C.elegans’ RNAi system is considered a “blanket system,” meaning that ithas parallels in humans, making the worm model discovered by Ding andhis colleagues a valuable tool in studying the way viruses interactwith hosts. This tool may speed the discovery of treatments forvirus-caused diseases that plague humans.
“The RNAi machinery isvery similar between humans and C. elegans, and human viruses such asInfluenza A virus and HIV are known to produce RNAi suppressors,” Dingsaid. “So now, the question is can we treat human viral diseases usingchemical inhibitors of viral RNAi suppressors?”
The methodsoutlined in the Nature paper are now being used to generate additionalC. elegans strains for screening chemical compounds that inactivateRNAi suppressors associated with avian flu, HIV and others.
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