A workhorse of modern biology is sick, and scientists couldn't be happier. Researchers at Washington University School of Medicine in St. Louis, the Jacques Monod Institute in France and Cambridge University have found that the nematode C. elegans, a millimeter-long worm used extensively for decades to study many aspects of biology, can be targeted by naturally occurring viral infections. The discovery means C. elegans is likely to help scientists study the way viruses and their hosts interact. The findings will be published next week in the online, open access journal PLoS Biology.
Marie-Anne Felix, a research director at the Centre National de la Recherche Scientifique (CNRS, France), who studies the evolution of nematodes at the Jacques Monod Institute, began the study by gathering C. elegans from rotting fruit in French orchards. Felix noted that some of her sample worms appeared to be sick. Treatment with antibiotics failed to cure them. She then repeated a classic biological experiment that led to the discovery of viruses. Sick worms were ground up and passed through a filter fine enough to remove any bacterial or parasitic infectious agents. A new batch of worms was exposed to the ground-up remains of the first batch. When the new batch got sick, a viral infection was likely to be present.
David Wang, associate professor of pathology and immunology and of molecular microbiology at Washington University School of Medicine in St. Louis, specializes in the identification of novel viruses. He found the worms had been suffering infections from two viruses related to nodaviruses, a class of viruses previously found to infect insects and fish. Nodaviruses are not currently known to infect humans. Tests showed one of the new viruses can infect the strain of C. elegans most commonly used in research.
"We can easily disable any of C. elegans' genes, confront the worm with a virus and watch to see if this makes the infection worse, better or has no effect," says Wang. "If it changes the worm's response to infection, we will look to see if similar genes are present in humans and other mammals."
Wang notes that several fundamental phenomena of human biology were first revealed using C. elegans - these include the ability of cells to self-destruct to prevent cancer, and the process of RNA interference, which operates to destroy double helices of RNA coming from outside the organism. RNA interference was discovered by Andy Fire and Craig Mello (Nobel Prize 2006) and is widely used as a tool to inactivate genes, yet its natural role in C. elegans remained a mystery. With the new truly nematode-infecting virus, Alyson Ashe, a researcher in the laboratory of Eric Miska at the Gurdon Institute, Cambridge, UK, provides the first evidence in a completely natural setting and without any artificial manipulations, that RNA interference in C. elegans has an important role in defending the worm against viral genes.
"Model organisms are essential to important steps forward in biology, and we're eager to see what C. elegans can teach us about the way hosts and viruses interact," Wang says.
Funding: This work was supported in part by the CNRS (Félix lab), National Institutes of Health grant U54 AI057160 to the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research (Wang lab), and a Cancer Research UK Programme Grant (Miska lab). DW holds an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. AA was supported by a fellowship from the Herchel-Smith Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests statement: Eric Miska's spouse is a member of the PloS Biology editorial staff; in accordance with the PLoS policy on competing interests she has been excluded from all stages of the review process for this article.
Citation: Felix M-A, Ashe A, Piffaretti J, Wu G, Nuez I, et al. (2011) Natural and Experimental Infection of Caenorhabditis Nematodes by Novel Viruses Related to Nodaviruses. PLoS Biol 9(1): e1000586. doi:10.1371/journal.pbio.1000586
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