title: A Polymorphism in the Processing Body Component Ge-1 Controls Resistance to a Naturally Occurring Rhabdovirus in Drosophila.
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.
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Chuan
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Magwire
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Florian
authors.initials: F
authors.lastname: Bayer
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Francis M
authors.initials: FM
authors.lastname: Jiggins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000821:virology; D005838:Genotype; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012209:Rhabdoviridae; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; C000607443:Ge-1 protein, Drosophila; D034741:RNA, Small Interfering