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We previously identified RNA viruses that infect the nematodes Caenorhabditis elegans and Caenorhabditis briggsae in a species-specific manner. Wild strains of both host species demonstrate ample variation in viral sensitivity. Here we use recombinant inbred lines and pool-sequencing approaches to genetically map a major resistance locus in the C. elegans MY10 strain, narrowing down its position by CRISPR\/Cas9-mediated recombination and testing candidates by genome editing. A rare non-synonymous polymorphism in the gtnt-1 gene, encoding a putative glycosyltransferase of the GT92 family, causes resistance to viral infection in MY10. Loss-of-function gtnt-1 alleles conferred host protection only at late developmental stages, highlighting the importance of multigenerational assays capturing the full course of viral infection and transmission. Viral resistance through gtnt-1 mutation occurred repeatedly in C. elegans, with diverse alleles each remaining at low frequency (&amp;lt;1%). Furthermore, leveraging closely related C. briggsae strains differing in viral susceptibility, we find that repeated loss-of-function alleles of the Cbr-gtnt-1 ortholog similarly enhanced resistance and host fitness upon infection. In conclusion, recurrent evolution in two host species of loss-of-function alleles of gtnt-1 orthologs leads to viral resistance. The gtnt-1 gene being conserved between Caenorhabditis species, these repeated inactivation events provide a case of transient ecological adaptation to a pathogen through recurrent mutation of the same gene in two species. The low population frequencies of resistant alleles point to a changing eco-evolutionary context that prevents their spread in populations.<\/jats:p>","DOI":"10.1093\/molbev\/msag208","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:13:06Z","timestamp":1786705986000},"source":"Crossref","is-referenced-by-count":0,"title":["Repeated mutation of a GT92 glycosyltransferase gene confers antiviral resistance in two\n                    <i>Caenorhabditis<\/i>\n                    species"],"prefix":"10.1093","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1218-9970","authenticated-orcid":false,"given":"Aur\u00e9lien","family":"Richaud","sequence":"first","affiliation":[{"name":"IBENS, Department of Biology, Ecole Normale Sup\u00e9rieure, CNRS, Inserm, PSL Research University , Paris 75005 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6468-1341","authenticated-orcid":false,"given":"Gaotian","family":"Zhang","sequence":"additional","affiliation":[{"name":"IBENS, Department of Biology, Ecole Normale Sup\u00e9rieure, CNRS, Inserm, PSL Research University , Paris 75005 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1302-9270","authenticated-orcid":false,"given":"Cigdem","family":"Alkan","sequence":"additional","affiliation":[{"name":"IBENS, Department of Biology, Ecole Normale Sup\u00e9rieure, CNRS, Inserm, PSL Research University , Paris 75005 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1085-1063","authenticated-orcid":false,"given":"Daria","family":"Martynow","sequence":"additional","affiliation":[{"name":"IBENS, Department of Biology, Ecole Normale Sup\u00e9rieure, CNRS, Inserm, PSL Research University , Paris 75005 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3756-4729","authenticated-orcid":false,"given":"Tony","family":"B\u00e9licard","sequence":"additional","affiliation":[{"name":"IBENS, Department of Biology, Ecole Normale Sup\u00e9rieure, CNRS, Inserm, PSL Research University , Paris 75005 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6892-7783","authenticated-orcid":false,"given":"Nanako","family":"Takeda","sequence":"additional","affiliation":[{"name":"IBENS, Department of Biology, Ecole Normale Sup\u00e9rieure, CNRS, Inserm, PSL Research University , Paris 75005 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