Model worm susceptible to virus

The model organism Caenorhabditis elegans may now be able to take a sick day. For the first time in nearly forty years of intense study, scientists have identified two new viruses that can infect the worms in the wild, opening up new avenues of research in host-virus interactions.

Caenorhabditis elegans
Image: Mary-Anne Félix, The Monod Institute

"It's a landmark study," said linkurl:Dennis Kim,;http://web.mit.edu/biology/www/facultyareas/facresearch/kim.html a biologist at the Massachusetts Institute of Technology, who was not involved in the study. "This is a definitive work on naturally-occurring viruses in C. elegans."The simple anatomy and two- to three-week lifespan of C. elegans have made it ideal for studying complex biological processes. Over the years, researchers have used it to study a variety of systems, such as neurological development, reproduction, and even immune function, feeding the worms bacteria to see how they responded to pathogens. But there was one thing researchers have always failed to do with C. elegans -- study viruses. They simply couldn't find a virus that would infect the worm.A rotting apple in Orsay, France, changed all that. In Orsay, a suburb southwest of Paris, linkurl:Mary-Anne Félix;http://www.ijm.fr/en/ijm/research/research-groups/nematode/ of the Jacques Monod Institute found what looked like sick C. elegans. She took the worms back to the lab and dosed them with antibiotics and anti-parasitic medications. The worms remained ill. If bacteria and parasites weren't the cause, Félix figured, then it had to be a virus.Félix ground up a sample of sick worms and passed them through a filter with holes no bigger than 0.2 µm. Bacteria, parasites, and C. elegans cells were too big to fit through the tiny holes, but viruses could freely pass through. Félix then let a batch of perfectly healthy C. elegans grow in this filtered liquid. Within a week, the healthy worms began showing the same subtle symptoms as the original worms.Other researchers have tried to experimentally infect C. elegans with their favorite virus and failed, said linkurl:David Wang,;http://f1000.com/thefaculty/member/8559340216994992 one of Félix's co-authors and a microbiologist at Washington University in St. Louis. "We found evidence of naturally evolved viruses" that infect C. elegans. To figure out what type of virus was making the worms sick, the team amplified and sequenced random bits of DNA and RNA from a mixture of ground-up sick C. elegans, and compared them to a database of known virus genomes. Further amplifying the suspected viral genetic segments, the researchers identified the viruses as two never before seen RNA viruses. Both of the viruses showed some similarities to viruses in the family Nodaviridae, known to infect insects and fish, but they were still quite different. "They're not closely related to any viruses that have been described before," Wang said. Further experiments showed that the newly identified viruses could infect a wide variety of both laboratory and wild-type strains of C. elegans from around the world. Attaching a fluorescent tag to the viral RNA, the researchers saw that the viruses mainly infected the intestines of the worms, suggesting that the virus may spread through the fecal/oral route.Regardless of how the virus travels from one worm to another, Wang sees the identification of these viruses as a powerful new tool for virologists. "Up until now, no one has been able to probe virus-host interactions with C. elegans," Wang said. Now, scientists may be able to discover new ways in which viruses and their hosts interact "due to the ease with which C. elegans can be manipulated," he said."The fun part is when you have this sort of phenomenon happening in a very genetically tractable system," Kim agreed. "We don't know what we'll be able to find."Still, worms aren't humans, Wang said. Some of the most powerful weapons of the human immune system, such as antibodies and T cells, evolved in mammals, not nematodes. Conversely, some of the host-virus interactions that researchers may discover, he added, may be specific to worms. M.A. Félix, et al., "Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses," PLoS Biology, 9(1): e1000586. doi:10.1371/journal.pbio.1000586, 2011.
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[17th August 2006]