A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein

Abstract

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.

Hunting Drosophila viruses from wild populations: A novel isolation approach and characterisation of viruses

“…Drosophila C virus (DCV), which is widely studied but rare in nature, is virulent, with infections in laboratory stocks causing the death of larvae and pupae, and flies injected with the virus dying within days [ 12 ]. Other viruses like Drosophila A virus (DAV) and the DNA viruses Drosophila innubila Nudivirus (DiNV) and Kallithea virus reduce host fecundity and kill their hosts, albeit at a slower rate than typically reported for DCV [ 8 , 13 , 14 ]. Some viruses, such as galbut virus and sigma virus, have less obvious symptoms [ 7 , 15 ].…”

Hunting Drosophila viruses from wild populations: a novel isolation approach and characterization of viruses

“…Drosophila C virus (DCV), which is widely studied but rare in nature, is virulent, with infections in laboratory stocks causing the death of larvae and pupae, and flies injected with the virus dying within days [12]. Other viruses like Drosophila A virus (DAV) and the DNA viruses Drosophila innubila Nudivirus (DiNV) and Kallithea virus (KV) reduce host fecundity and kill their hosts, albeit at a slower rate than typically reported for DCV [8, 13, 14]. Some viruses, such as Galbut virus and sigma virus, have less obvious symptoms [12].…”

An extended Tudor domain within Vreteno interconnects Gtsf1L and Ago3 for piRNA biogenesis inBombyx mori

“…Notably, the expression of two Vreteno isoforms seems to be restricted to silkworm. However, in addition to Vreteno, flies also express a Vreteno-like protein in their ovaries, which is called Veneno (Brosh et al, 2022).…”

“…Notably, the expression of two Vreteno isoforms seems to be restricted to silkworm. However, in addition to Vreteno, flies also express a Vreteno-like protein in their ovaries, which is called Veneno (Brosh et al , 2022). DmVeneno has a very similar domain architecture compared to DmVreteno but is lacking an N-terminal RRM and, as such, mimics the domain organization of the BmVreteno-S isoform (Nishida et al , 2020; Brosh et al , 2022).…”