Orsay Virus infection dynamics in Caenorhabditis elegans

The recently discovered Orsay virus (OrV) is the first virus able to complete a full infection cycle in the nematode C. elegans. This discovery creates the opportunity to study host-virus interactions in a genetically tractable host system. OrV is transmitted horizontally and antiviral RNAi was indicated to play a role during infection. Here we report a quantitative study of OrV replication and the trans-generational effects of anti-viral (RNAi) mechanisms in C. elegans. By infecting worm cohorts at different time points with OrV, progression of infection was monitored through quantification of viral RNA using qPCR. The influence of worm age and genotype on viral replication was determined. We found an age-related resistance to OrV infection and a faster replication in the wild isolate JU1580 (in which OrV was first identified) than in the canonical strain Bristol N2. In RNAi mutants in an N2 background the infection progressed considerably faster. Next, several subsequent generations exposed to virus were re-infected to determine if trans-generational effects plays a role in infections in C. elegans populations. These experiments showed that the RNAi response also plays a trans-generational role by making offspring of infected N2 less susceptible to viral replication. Consequently, N2 populations can lose the infection after a limited number of generations, whereas JU1580 populations remain infected. A dual role for the RNAi response was found. Firstly by limiting the initial infection, both in speed and viral load. Secondly by providing an inherited protection against infection. This establishes the heritable RNAi response as anti-viral mechanism during natural virus infections in C. elegans.