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Relative to murine infections, little is known about which parasite effectors disarm human immune responses. Here, we used targeted CRISPR screening to identify secreted protein effectors required for parasite survival in IFN\u03b3-activated human cells. Independent screens were carried out using 2 <jats:italic>Toxoplasma<\/jats:italic> strains that differ in virulence in mice, leading to the identification of effectors required for survival in IFN\u03b3-activated human cells. We identify the secreted protein GRA57 and 2 other proteins, GRA70 and GRA71, that together form a complex which enhances the ability of parasites to persist in IFN\u03b3-activated human foreskin fibroblasts (HFFs). Components of the protein machinery required for export of <jats:italic>Toxoplasma<\/jats:italic> proteins into the host cell were also found to be important for parasite resistance to IFN\u03b3 in human cells, but these export components function independently of the identified protein complex. Host-mediated ubiquitination of the parasite vacuole has previously been associated with increased parasite clearance from human cells, but we find that vacuoles from GRA57, GRA70, and GRA71 knockout strains are surprisingly less ubiquitinated by the host cell. We hypothesise that this is likely a secondary consequence of deletion of the complex, unlinked to the IFN\u03b3 resistance mediated by these effectors.<\/jats:p>","DOI":"10.1371\/journal.pbio.3002202","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T17:32:49Z","timestamp":1689615169000},"page":"e3002202","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["A heterotrimeric complex of Toxoplasma proteins promotes parasite survival in interferon gamma-stimulated human cells"],"prefix":"10.1371","volume":"21","author":[{"given":"Eloise J.","family":"Lockyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Torelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Butterworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ok-Ryul","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Howell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Weston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"East","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-6657","authenticated-orcid":true,"given":"Moritz","family":"Treeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"issue":"7","key":"pbio.3002202.ref001","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2471\/BLT.12.111732","article-title":"The global burden of congenital toxoplasmosis: a systematic review","volume":"91","author":"PR Torgerson","year":"2013","journal-title":"Bull World Health Organ"},{"key":"pbio.3002202.ref002","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.pt.2010.01.009","article-title":"Toxoplasma gondii: epidemiology, feline clinical aspects, and prevention","author":"SA Elmore","year":"2010","journal-title":"Trends Parasitol"},{"key":"pbio.3002202.ref003","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.chom.2014.01.004","article-title":"Innate resistance against Toxoplasma gondii: An evolutionary tale of mice, cats, and men","author":"RT Gazzinelli","year":"2014","journal-title":"Cell Host Microbe. 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in Interferon Gamma-Stimulated Human Cells","author":"S Krishnamurthy","year":"2023","journal-title":"MBio"},{"issue":"1","key":"pbio.3002202.ref072","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.molbiopara.2006.05.003","article-title":"Anticoccidial kinase inhibitors: Identification of protein kinase targets secondary to cGMP-dependent protein kinase","volume":"149","author":"RGK Donald","year":"2006","journal-title":"Mol Biochem Parasitol"},{"key":"pbio.3002202.ref073","article-title":"Structural cells are key regulators of organ-specific immune responses","author":"T Krausgruber","year":"2020","journal-title":"Nature"},{"issue":"1","key":"pbio.3002202.ref074","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-022-32225-z","article-title":"IFN-\u03b3 stimulated murine and human neurons mount anti-parasitic defenses against the intracellular parasite Toxoplasma gondii","volume":"13","author":"S Chandrasekaran","year":"2022","journal-title":"Nat 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DeepTMHMM predicts alpha and beta transmembrane proteins using deep neural networks. 2022."},{"issue":"Web Server issue","key":"pbio.3002202.ref086","doi-asserted-by":"crossref","first-page":"W408","DOI":"10.1093\/nar\/gkv451","article-title":"CCTOP: a Consensus Constrained TOPology prediction web server","volume":"43","author":"L Dobson","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pbio.3002202.ref087","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1093\/bioinformatics\/btu700","article-title":"Waggawagga: comparative visualization of coiled-coil predictions and detection of stable single \u03b1-helices (SAH domains)","volume":"31","author":"D Simm","year":"2015","journal-title":"Bioinformatics"},{"issue":"1","key":"pbio.3002202.ref088","first-page":"1","article-title":"RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"B Li","year":"2011","journal-title":"BMC Bioinformatics"},{"issue":"3","key":"pbio.3002202.ref089","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41587-020-0439-x","article-title":"The nf-core framework for community-curated bioinformatics pipelines","volume":"38","author":"PA Ewels","year":"2020","journal-title":"Nature Biotechnol"},{"key":"pbio.3002202.ref090","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","author":"MI Love","year":"2014","journal-title":"Genome Biol"}],"updated-by":[{"DOI":"10.1371\/journal.pbio.3002202","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000}}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3002202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T18:01:51Z","timestamp":1690480911000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3002202"}},"subtitle":[],"editor":[{"given":"Kami","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,17]]},"references-count":90,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3002202","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pbio.3002202","asserted-by":"object"}]},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,17]]}}}