Abstract
Background Genetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation present for an antiviral pathway, the Intracellular Pathogen Response (IPR), underlying susceptibility to Orsay virus in the model organism Caenorhabditis elegans. The IPR involves transcriptional activity of 80 genes including the pals-genes. The pals-genes form an expanded gene family which hints they could be shaped by an evolutionary selective pressure. Here we examine the genetic variation in the pals-family for traces of selection and explore the molecular and phenotypic effects of having distinct pals-gene alleles.
Results Genetic analysis of 330 world-wide C. elegans strains reveals that genetic diversity within the IPR-related pals-genes can be categorized in a few haplotypes worldwide. Importantly, two key-IPR regulators, pals-22 and pals-25, are in a genomic region carrying signatures of balancing selection. Therefore, distinct pals-22/pals-25 alleles have been maintained in C. elegans populations over time, which suggests different evolutionary strategies exist in IPR regulation. We investigated the IPR by infecting two C. elegans strains that represent distinct pals-22/pals-25 haplotypes, N2 and CB4856, with Orsay virus to determine their susceptibility and transcriptional response to infection. Our data suggests that regulatory genetic variation underlies constant high activity of IPR genes in CB4856 which could determine the host transcriptional defense. We found that CB4856 shows initially lower viral susceptibility than N2. High basal IPR expression levels might help counteract viral infection directly, whereas N2-like strains that need to activate the IPR genes first may have a slower response. Nevertheless, most wild strains harbor N2-like alleles for the pals-genes.
Conclusions Our work provides evidence for balancing genetic selection of immunity genes in C. elegans and illustrated how this may shape the transcriptional defense against pathogens. The transcriptional and genetic data presented in this study therefore provide a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
After submission to a journal leading to rejection, we have addressed the concerns of the reviewers and restructured the paper, included new experiments and streamlined the gene expression analyses.
Abbreviations
- FDR
- False Discovery Rate
- FISH
- Fluorescent In Situ Hybridization
- IPR
- Intracellular Pathogen Response
- OrV
- Orsay virus
- PCA
- Principal Component Analysis
- QTL
- Quantitative Trait Locus
- RNAi
- RNA interference
- RT-qPCR
- Reverse Transcription-quantitative PCR