Researchers have found that the nematode Caenorhabditis elegans, a millimeter-long worm used extensively for decades to study many aspects of biology, can be targeted by naturally occurring virus infections. The discovery means C. elegans is likely to help scientists study the way viruses and their hosts interact.
Marie-Anne Felix 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, at Washington University School of Medicine in St. Louis, 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.
Several fundamental phenomena of human biology were first revealed using C. elegans – including 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. The new nematode-infecting virus 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 viruses.
“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. “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.”
Natural and Experimental Infection of Caenorhabditis Nematodes by Novel Viruses Related to
Nodaviruses. (2011) PLoS Biol 9(1): e1000586. doi:10.1371/journal.pbio.1000586
An ideal model system to study antiviral immunity and host-pathogen co-evolution would combine a genetically tractable small animal with a virus capable of naturally infecting the host organism. The use of C. elegans as a model to define host- viral interactions has been limited by the lack of viruses known to infect nematodes. From wild isolates of C. elegans and C. briggsae with unusual morphological phenotypes in intestinal cells, we identified two novel RNA viruses distantly related to known nodaviruses, one infecting specifically C. elegans (Orsay virus), the other C. briggsae (Santeuil virus). Bleaching of embryos cured infected cultures demonstrating that the viruses are neither stably integrated in the host genome nor transmitted vertically. 0.2 mm filtrates of the infected cultures could infect cured animals. Infected animals continuously maintained viral infection for 6 mo (50 generations), demonstrating that natural cycles of horizontal virus transmission were faithfully recapitulated in laboratory culture. In addition to infecting the natural C. elegans isolate, Orsay virus readily infected laboratory C. elegans mutants defective in RNAi and yielded higher levels of viral RNA and infection symptoms as compared to infection of the corresponding wild-type N2 strain. These results demonstrated a clear role for RNAi in the defense against this virus. Furthermore, different wild C. elegans isolates displayed differential susceptibility to infection by Orsay virus, thereby affording genetic approaches to defining antiviral loci. This discovery establishes a bona fide viral infection system to explore the natural ecology of nematodes, host-pathogen co-evolution, the evolution of small RNA responses, and innate antiviral mechanisms.