Brosh, O., Fabian, D.K., Cogni, R., Tolosana, I., Day, J.P., Olivieri, F., Merckx, M., Akilli, N., Szkuta, P., Jiggins, F.M. (2022). A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein.  Proc. Natl. Acad. Sci. U.S.A. 119(29): e2122026119.

FBrf0254052

Research paper

Hosts are continually selected to evolve new defenses against an ever-changing array of pathogens. To understand this process, we examined the genetic basis of resistance to the Drosophila A virus in Drosophila melanogaster. In a natural population, we identified a polymorphic transposable element (TE) insertion that was associated with an ∼19,000-fold reduction in viral titers, allowing flies to largely escape the harmful effects of infection by this virulent pathogen. The insertion occurs in the protein-coding sequence of the gene Veneno, which encodes a Tudor domain protein. By mutating Veneno with CRISPR-Cas9 in flies and expressing it in cultured cells, we show that the ancestral allele of the gene has no effect on viral replication. Instead, the TE insertion is a gain-of-function mutation that creates a gene encoding a novel resistance factor. Viral titers remained reduced when we deleted the TE sequence from the transcript, indicating that resistance results from the TE truncating the Veneno protein. This is a novel mechanism of virus resistance and a new way by which TEs can contribute to adaptation.

PMC9304006 (PMC) (EuropePMC)