Abstract
Hosts encounter an ever-changing array of pathogens, so there is continual selection for novel ways to resist infection. A powerful way to understand how hosts evolve resistance is to identify the genes that cause variation in susceptibility to infection. Using high-resolution genetic mapping we have identified a naturally occurring polymorphism in a gene called Ge-1 that makes Drosophila melanogaster highly resistant to its natural pathogen Drosophila melanogaster sigma virus (DMelSV). By modifying the sequence of the gene in transgenic flies, we identified a 26 amino acid deletion in the serine-rich linker region of Ge-1 that is causing the resistance. Knocking down the expression of the susceptible allele leads to a decrease in viral titre in infected flies, indicating that Ge-1 is an existing restriction factor whose antiviral effects have been increased by the deletion. Ge-1 plays a central role in RNA degradation and the formation of processing bodies (P bodies). A key effector in antiviral immunity, the RNAi induced silencing complex (RISC), localises to P bodies, but we found that Ge-1-based resistance is not dependent on the small interfering RNA (siRNA) pathway. However, we found that Decapping protein 1 (DCP1) protects flies against sigma virus. This protein interacts with Ge-1 and commits mRNA for degradation by removing the 5’ cap, suggesting that resistance may rely on this RNA degradation pathway. The serine-rich linker domain of Ge-1 has experienced strong selection during the evolution of Drosophila, suggesting that this gene may be under long-term selection by viruses. These findings demonstrate that studying naturally occurring polymorphisms that increase resistance to infections enables us to identify novel forms of antiviral defence, and support a pattern of major effect polymorphisms controlling resistance to viruses in Drosophila.
Highlights
Hosts and their pathogens are engaged in a never-ending arms race, where the evolution of new defences in turn selects for pathogens that can overcome those defences
In flies that are highly resistant to a naturally occurring virus called sigma virus we identified a deletion in the protein-coding region of a gene called Ge-1
We show that even the susceptible allele of Ge-1 helps protect flies against the virus, suggesting that this mutation has made an existing antiviral defence more effective
Summary
Hosts and their pathogens are engaged in a never-ending arms race, where the evolution of new defences in turn selects for pathogens that can overcome those defences. In order to understand how hosts are evolving resistance, it is necessary to investigate the genes that cause variation in the susceptibility to infection in the wild. Resistance can evolve by altering the host immune defences, and by changing host factors that are hijacked by the pathogen for its own benefit. Viruses are important pathogens of insects, but the antiviral defences of insects are still comparatively poorly understood. Several other pathways and the endosymbiotic bacterium Wolbachia have been implicated in the antiviral immunity in Drosophila [6,7,8,9,10,11,12,13,14,15,16], but these are mostly relatively poorly understood
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