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.
Original language | English |
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Article number | 758331 |
Journal | Frontiers in Cellular and Infection Microbiology |
Volume | 11 |
DOIs | |
Publication status | Published - 31 Jan 2022 |
Keywords
- balancing selection
- Caenorhabditis elegans
- intracellular pathogen response
- Orsay virus
- pals-22
- pals-25
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Microarray on Caenorhabditis elegans N2 and CB4856 infected with Orsay virus
Sterken, M. G. (Creator), Wageningen University & Research, 8 Jul 2020
https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-7574/
Dataset
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Microarray of C. elegans wild types N2 and CB4856 after Orsay virus infection and heat-shock treatment
Sterken, M. (Creator), Wageningen University & Research, 15 Mar 2021
https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-10214/
Dataset
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Microarray on an infection time-series of Orsay virus in three Caenorhabditis elegans genotypes
Sterken, M. G. (Creator), Wageningen University & Research, 14 Jul 2020
https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-7573/
Dataset