Abstract
Genetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation in the Intracellular Pathogen Response (IPR), an important antiviral pathway in the model organism Caenorhabditis elegans against Orsay virus (OrV). The IPR involves transcriptional activity of 80 genes including the pals-genes. 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. Genetic analysis of 330 global 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, suggesting that different evolutionary strategies exist in IPR regulation. We infected eleven C. elegans strains that represent three distinct pals-22 pals-25 haplotypes with Orsay virus to determine their susceptibility. For two of these strains, N2 and CB4856, the transcriptional response to infection was also measured. The results indicate that pals-22 pals-25 haplotype shapes the defense against OrV and host genetic variation can result in constitutive activation of IPR genes. Our work presents evidence for balancing genetic selection of immunity genes in C. elegans and provides a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations.
Highlights
Viral infections occur in natural populations of all organisms
Viral susceptibility can be determined by host genetic variation
Our findings show that genetic variation in C. elegans affects the Intracellular Pathogen Response (IPR): a transcriptional response that counteracts pathogens by increased proteostasis and in which at least 27 pals-genes are involved (Reddy et al, 2017; Reddy et al, 2019)
Summary
Viral infections occur in natural populations of all organisms. Genetic variation can change hostvirus interactions by altering coding sequences of protein products. Host-virus interactions can be influenced by genetic variation due to altered gene copy numbers. Structural and regulatory genetic variation may both affect the viral susceptibility after infection, making some individuals within the population more resistant than others (Franco et al, 2013; Frontiers in Cellular and Infection Microbiology | www.frontiersin.org van Sluijs et al. Balancing Selection on C. elegans IPR van Sluijs et al, 2017; Piasecka et al, 2018; Wang et al, 2018). Presence of viruses can thereby select for beneficial genetic variants to remain present in the population (Enard et al, 2016; Wilke and Sawyer, 2016)
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