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In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent<jats:italic>T. gondii<\/jats:italic>strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1<jats:sub>CIM<\/jats:sub>to the<jats:italic>T. gondii<\/jats:italic>virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American<jats:italic>T. gondii<\/jats:italic>strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1<jats:sub>CIM<\/jats:sub>, indicating co-adaptation of host cell resistance GTPases and<jats:italic>T. gondii<\/jats:italic>virulence effectors.<\/jats:p>","DOI":"10.1038\/s41467-019-09200-2","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T11:02:32Z","timestamp":1552647752000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-3612","authenticated-orcid":false,"given":"Mateo","family":"Murillo-Le\u00f3n","sequence":"first","affiliation":[]},{"given":"Urs B.","family":"M\u00fcller","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8620-4095","authenticated-orcid":false,"given":"Ines","family":"Zimmermann","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-3992","authenticated-orcid":false,"given":"Shishir","family":"Singh","sequence":"additional","affiliation":[]},{"given":"Pia","family":"Widdershooven","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1809-8272","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Campos","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8721-3038","authenticated-orcid":false,"given":"Catalina","family":"Alvarez","sequence":"additional","affiliation":[]},{"given":"Stephanie","family":"K\u00f6nen-Waisman","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-3931","authenticated-orcid":false,"given":"Nahleen","family":"Lukes","sequence":"additional","affiliation":[]},{"given":"Zsolt","family":"Ruzsics","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2756-5143","authenticated-orcid":false,"given":"Jonathan C.","family":"Howard","sequence":"additional","affiliation":[]},{"given":"Martin","family":"Schwemmle","sequence":"additional","affiliation":[]},{"given":"Tobias","family":"Steinfeldt","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,3,15]]},"reference":[{"key":"9200_CR1","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1128\/CMR.00005-17","volume":"30","author":"MA Hakimi","year":"2017","unstructured":"Hakimi, M. 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