A Polymorphism in the Processing Body Component Ge-1 Controls Resistance to a Naturally Occurring Rhabdovirus in Drosophila

PLoS Pathog. 2016 Jan 22;12(1):e1005387. doi: 10.1371/journal.ppat.1005387. eCollection 2016 Jan.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Carrier Proteins / genetics*
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / virology
  • Genotype
  • Molecular Sequence Data
  • Polymorphism, Genetic*
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhabdoviridae*
  • Transfection


  • Carrier Proteins
  • Drosophila Proteins
  • Ge-1 protein, Drosophila
  • RNA, Small Interfering