Dissecting the genetic architecture of resistance to orsay virus infection in C. elegans

Host-pathogen interactions play a major role in evolutionary selection and in shaping natural genetic variation. Recent identification of viral infection in C. elegans has prompted research into understanding the underlying pathways of Orsay virus (OrV) infection in natural populations. Here we report the dissection of the genetic architecture of OrV infection. We found that wild type Hawaii CB4856 strain was more resistant to OrV than the canonical Bristol N2 strain. To gain insight into the genetic architecture of resistance, 52 fully sequenced recombinant inbred lines (CB4856 x N2 RILs) were exposed to OrV using our recently developed quantitative assay. This led to the identification of two distinct loci on chromosome IV associated with OrV resistance. These loci were both associated with a lower viral load in the CB4856 genotype. Strikingly, these loci do not harbour the recently found drh-1 locus, which encodes a RIG-I like helicase that plays an important role in antiviral RNAi. To verify our results and gain additional insight into the genetic architecture, a panel of 18 introgression lines (ILs) (together covering chromosome IV entirely) was exposed to OrV. Both loci could be verified by ILs, also showing more resistance against OrV infection with the CB4856 locus. Our results provide insight in the loci underlying the higher viral resistance in CB4856. They also form an important step toward identifying polymorphic genes underlying resistance to viral infection in C. elegans.