RNA interference protects worms from viruses

Caenorhabditis elegans (C. elegans) is a small worm (~1000 cells) that is widely used to study development. There are no known natural viral pathogens of C. elegans. Wilkins and colleagues suspected a protective role for RNA interference (RNAi), an anti-viral system that was discovered in plants and subsequently implicated in insect immunity. RNAi acts through small interfering RNA (siRNA) that matches the target sequence (animation from Nature). They tried infecting primary cell cultures with vesicular stomatitis virus (VSV), which is a negative sense RNA virus with a broad host range. To make the measurement easier, they used a virus marked with green fluorescent protein (VSV-GFP). The system worked: replication competent viruses infected wild-type worm cells. Infection could be monitored by fluorescence or by measuring the virus transcripts. Cells from two different mutants defective in RNAi -- one (eri-1) that reduces siRNA cleavage and a second (rrf-3) that permits siRNA amplification -- supported higher levels of virus infection and amplification. Moreover, they could detect a 20-30 nucleotide endogenous siRNA that matches the VSV nucleoprotein. They conclude that RNAi blocks virus replication and reduces virus infection and expression.
Wilkins C, Dishongh R, Moore SC, Whitt MA, Chow M, Machaca K. "RNA interference is an antiviral defence mechanism in Caenorhabditis elegans." Nature. 2005 Aug 18; 436(7053):1044-7.