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In vertebrates, these genes include interferons that play a critical role in the amplification of the response to infection. Virus- and interferon-stimulated genes include restriction factors targeting the different steps of the viral replication cycle, in addition to molecules associated with inflammation and adaptive immunity. Predictably, antiviral genes evolve dynamically in response to viral pressure. As a result, each animal has a unique arsenal of antiviral genes. Here, we exploit the capacity to experimentally activate the evolutionarily conserved stimulator of IFN genes (STING) signaling pathway by injection of the cyclic dinucleotide 2\u20323\u2032-cyclic guanosine monophosphate-adenosine monophosphate into flies to define the repertoire of STING-regulated genes in 10 Drosophila species, spanning 40 million years of evolution. Our data reveal a set of conserved STING-regulated factors, including STING itself, a cGAS-like-receptor, the restriction factor pastel, and the antiviral protein Vago, but also 2 key components of the antiviral RNA interference pathway, Dicer-2, and Argonaute2. In addition, we identify unknown species- or lineage-specific genes that have not been previously associated with resistance to viruses. Our data provide insight into the core antiviral response in Drosophila flies and pave the way for the characterization of previously unknown antiviral effectors.<\/jats:p>","DOI":"10.1093\/molbev\/msae032","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T19:49:22Z","timestamp":1708458562000},"source":"Crossref","is-referenced-by-count":11,"title":["Investigating the Evolution of <i>Drosophila<\/i> STING-Dependent Antiviral Innate Immunity by Multispecies Comparison of 2\u20323\u2032-cGAMP Responses"],"prefix":"10.1093","volume":"41","author":[{"given":"L\u00e9na","family":"H\u00e9delin","sequence":"first","affiliation":[{"name":"CNRS UPR9022, Institut de Biologie Mole\u0301culaire et Cellulaire, Universite\u0301 de Strasbourg , Strasbourg , France"}]},{"given":"Antonin","family":"Thi\u00e9baut","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolution, SIB Swiss Institute of Bioinformatics, University of Lausanne , Lausanne , Switzerland"}]},{"given":"Jingxian","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science, Sino-French Hoffmann Institute, Guangzhou Medical University , Guangzhou , China"}]},{"given":"Xiaoyan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science, Sino-French Hoffmann Institute, Guangzhou Medical University , Guangzhou , China"}]},{"given":"Aur\u00e9lie","family":"Lemoine","sequence":"additional","affiliation":[{"name":"CNRS UPR9022, Institut de Biologie Mole\u0301culaire et Cellulaire, Universite\u0301 de Strasbourg , Strasbourg , France"}]},{"given":"Gabrielle","family":"Haas","sequence":"additional","affiliation":[{"name":"CNRS UPR9022, Institut de Biologie Mole\u0301culaire et Cellulaire, Universite\u0301 de Strasbourg , Strasbourg , France"}]},{"given":"Carine","family":"Meignin","sequence":"additional","affiliation":[{"name":"CNRS UPR9022, Institut de Biologie Mole\u0301culaire et Cellulaire, Universite\u0301 de Strasbourg , Strasbourg , France"}]},{"given":"Hua","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science, Sino-French Hoffmann Institute, Guangzhou Medical University , Guangzhou , China"}]},{"given":"Robert M","family":"Waterhouse","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolution, SIB Swiss Institute of Bioinformatics, University of Lausanne , Lausanne , Switzerland"}]},{"given":"Nelson","family":"Martins","sequence":"additional","affiliation":[{"name":"CNRS UPR9022, Institut de Biologie Mole\u0301culaire et Cellulaire, Universite\u0301 de Strasbourg , Strasbourg , France"}]},{"given":"Jean-Luc","family":"Imler","sequence":"additional","affiliation":[{"name":"CNRS UPR9022, Institut de Biologie Mole\u0301culaire et Cellulaire, Universite\u0301 de Strasbourg , Strasbourg , France"},{"name":"School of Basic Medical Science, Sino-French Hoffmann Institute, Guangzhou Medical University , Guangzhou , China"}]}],"member":"286","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"issue":"6431","key":"2024032920270604300_msae032-B1","doi-asserted-by":"crossref","first-page":"eaat8657","DOI":"10.1126\/science.aat8657","article-title":"cGAS in action: expanding roles in immunity and inflammation","volume":"363","author":"Ablasser","year":"2019","journal-title":"Science"},{"issue":"6","key":"2024032920270604300_msae032-B2","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1016\/j.celrep.2020.01.021","article-title":"A requirement for argonaute 4 in mammalian antiviral defense","volume":"30","author":"Adiliaghdam","year":"2020","journal-title":"Cell Rep"},{"issue":"6","key":"2024032920270604300_msae032-B3","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/wrna.1361","article-title":"Virus-derived small RNAs: molecular footprints of host-pathogen interactions","volume":"7","author":"Aguiar","year":"2016","journal-title":"Wiley Interdiscip Rev RNA"},{"issue":"32","key":"2024032920270604300_msae032-B4","doi-asserted-by":"crossref","first-page":"13410","DOI":"10.1073\/pnas.0811087106","article-title":"Nine exceptional radiations plus high turnover explain species diversity in jawed vertebrates","volume":"106","author":"Alfaro","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024032920270604300_msae032-B5","author":"Andrews","year":"2010"},{"key":"2024032920270604300_msae032-B6","author":"Aphalo","year":"2023"},{"issue":"9","key":"2024032920270604300_msae032-B7","doi-asserted-by":"crossref","first-page":"e54458","DOI":"10.15252\/embr.202154458","article-title":"Sequestration of LINE-1 in cytosolic aggregates by MOV10 restricts retrotransposition","volume":"23","author":"Arora","year":"2022","journal-title":"EMBO Rep"},{"key":"2024032920270604300_msae032-B8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.coviro.2014.03.010","article-title":"The long and short of antiviral 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Biol Chem"},{"key":"2024032920270604300_msae032-B40","author":"Imler"},{"issue":"5","key":"2024032920270604300_msae032-B41","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/evl3.247","article-title":"Between virus correlations in the outcome of infection across host species: evidence of virus by host species interactions","volume":"5","author":"Imrie","year":"2021","journal-title":"Evol Lett"},{"issue":"3","key":"2024032920270604300_msae032-B42","doi-asserted-by":"crossref","first-page":"267","DOI":"10.5802\/crbiol.37","article-title":"Insect decline: immediate action is needed","volume":"343","author":"Jactel","year":"2021","journal-title":"C R Biol"},{"issue":"6","key":"2024032920270604300_msae032-B43","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.4049\/jimmunol.1600994","article-title":"Charon mediates immune deficiency\u2013driven PARP-1\u2013dependent immune responses in Drosophila","volume":"197","author":"Ji","year":"2016","journal-title":"J 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Immunol."},{"issue":"4","key":"2024032920270604300_msae032-B49","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat Methods"},{"issue":"2","key":"2024032920270604300_msae032-B50","doi-asserted-by":"crossref","first-page":"e02777-19","DOI":"10.1128\/mBio.02777-19","article-title":"A sustained immune response supports long-term antiviral immune priming in the pacific oyster, crassostrea gigas","volume":"11","author":"Lafont","year":"2020","journal-title":"mBio"},{"issue":"3","key":"2024032920270604300_msae032-B51","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1073\/pnas.1516122113","article-title":"Cytokine diedel and a viral homologue suppress the IMD pathway in Drosophila","volume":"113","author":"Lamiable","year":"2016","journal-title":"Proc Natl Acad Sci U S 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