A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein.
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Authors
Brosh, Osama
Cogni, Rodrigo
Day, Jonathan P
Olivieri, Francesca
Akilli, Nazli
Szkuta, Piotr
Publication Date
2022-07-19Journal Title
Proc Natl Acad Sci U S A
ISSN
0027-8424
Publisher
Proceedings of the National Academy of Sciences
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Brosh, O., Fabian, D. K., Cogni, R., Tolosana, I., Day, J. P., Olivieri, F., Merckx, M., et al. (2022). A novel transposable element-mediated mechanism causes antiviral resistance in Drosophila through truncating the Veneno protein.. Proc Natl Acad Sci U S A https://doi.org/10.1073/pnas.2122026119
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.
Keywords
Drosophila, Tudor domain, adaptation, transposable element, virus, Animals, DNA Transposable Elements, Dicistroviridae, Drosophila melanogaster, Gain of Function Mutation, Host-Pathogen Interactions, Sequence Deletion, Tudor Domain
Relationships
Is supplemented by: https://doi.org/10.17863/CAM.84829
Sponsorship
This work was funded by grants from the Natural Environment Research Council (NE/P00184X/1) and the Leverhulme Trust (RPG-2020-236) to FJ. RC is funded by the São Paulo Research Foundation (FAPESP) (2013/25991-0 and 2015/08307-3), the National Council for Scientific and Technological Development (CNPq) (307447/2018-9) and a Newton Advanced Fellowship from the Royal Society (NAF\R1\180244). OB is funded by the Dr. Herchel Smith Fellowship.
Funder references
Natural Environment Research Council (NE/P00184X/1)
Leverhulme Trust (RPG-2020-236)
Identifiers
External DOI: https://doi.org/10.1073/pnas.2122026119
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337566
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