{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T21:54:36Z","timestamp":1747173276716,"version":"3.40.5"},"reference-count":56,"publisher":"Cambridge University Press (CUP)","issue":"13","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> rhoptry protein <jats:italic>Tg<\/jats:italic>ROP18 is a polymorphic virulence effector that targets immunity-related GTPases (IRGs) in rodents. Given that IRGs are uniquely diversified in rodents and not in other <jats:italic>T. gondii<\/jats:italic> intermediate hosts, the role of <jats:italic>Tg<\/jats:italic>ROP18 in manipulating non-rodent cells is unclear. Here we show that in human cells <jats:italic>Tg<\/jats:italic>ROP18<jats:sub>I<\/jats:sub> interacts with the interferon-gamma-inducible protein N-myc and STAT interactor (NMI) and that this is a property that is unique to the type I <jats:italic>Tg<\/jats:italic>ROP18 allele. Specifically, when expressed ectopically in mammalian cells only <jats:italic>Tg<\/jats:italic>ROP18<jats:sub>I<\/jats:sub> co-immunoprecipitates with NMI in IFN-\u03b3-treated cells, while <jats:italic>Tg<\/jats:italic>ROP18<jats:sub>II<\/jats:sub> does not. In parasites expressing <jats:italic>Tg<\/jats:italic>ROP18<jats:sub>I<\/jats:sub> or <jats:italic>Tg<\/jats:italic>ROP18<jats:sub>II<\/jats:sub>, NMI only co-immunoprecipitates with TgROP18<jats:sub>I<\/jats:sub> and this is associated with allele-specific immunolocalization of NMI on the parasitophorous vacuolar membrane (PVM). We also found that <jats:italic>Tg<\/jats:italic>ROP18<jats:sub>I<\/jats:sub> reduces NMI association with IFN-\u03b3-activated sequences (GAS) in the <jats:italic>IRF1<\/jats:italic> gene promoter. Finally, we determined that polymorphisms in the C-terminal kinase domain of <jats:italic>Tg<\/jats:italic>ROP18<jats:sub>I<\/jats:sub> are required for allele-specific effects on NMI. Together, these data further define new host pathway targeted by <jats:italic>Tg<\/jats:italic>ROP18<jats:sub>I<\/jats:sub> and provide the first function driven by allelic differences in the highly polymorphic <jats:italic>ROP18<\/jats:italic> locus.<\/jats:p>","DOI":"10.1017\/s0031182020001249","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T10:31:56Z","timestamp":1596105116000},"page":"1433-1442","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":3,"title":["Strain-specific disruption of interferon-stimulated N-myc and STAT interactor (NMI) function by <i>Toxoplasma gondii<\/i> type I ROP18 in human cells"],"prefix":"10.1017","volume":"147","author":[{"given":"Jing","family":"Xia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew 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