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Talents","award":["SXBYKY2024025"],"award-info":[{"award-number":["SXBYKY2024025"]}]},{"name":"the Special Research Fund of Shanxi Agricultural University for High-level Talents","award":["RFSXIHLT202101"],"award-info":[{"award-number":["RFSXIHLT202101"]}]},{"name":"the Special Research Fund of Shanxi Agricultural University for High-level Talents","award":["2021XG001"],"award-info":[{"award-number":["2021XG001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Toxoplasma gondii is a globally prevalent parasite capable of establishing lifelong infections, which can have severe consequences in immunocompromised individuals and developing fetuses. GRAs are essential secretory effectors that facilitate nutrient acquisition, modulate host immune responses, and support intracellular survival. In this study, we characterized four putative GRAs (GRA85\u201388) that co-localize with GRA12 in both tachyzoite and bradyzoite stages. Using CRISPR-Cas9-mediated homologous recombination, we successfully generated knockout strains in both type I RH and type II Pru backgrounds. Phenotypic analysis revealed that GRA85, GRA87, and GRA88 were not individually required for parasite replication, invasion, or virulence. However, deletion of gra86 (Pru\u0394gra86) resulted in a significant reduction in virulence and fewer brain cysts in chronically infected mice, although in vitro growth remained unaffected. Transcriptomic profiling of Pru\u0394gra86 revealed downregulation of bradyzoite\u2013related genes and upregulation of GRAs involved in host interaction. Additionally, in vitro differentiation assays showed impaired bradyzoite development in the absence of GRA86. These findings from murine models and in vitro phenotypic assays highlight GRA86 as a regulator of chronic infection and stage conversion, positioning it as an important player in T. gondii pathogenesis and a promising target for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ani15172591","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T08:08:46Z","timestamp":1756973326000},"page":"2591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["GRA86 Is a Novel Dense Granule Protein Important for Virulence and Bradyzoite Differentiation in Toxoplasma gondii"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6224-3603","authenticated-orcid":false,"given":"Xiao-Nan","family":"Zheng","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1528-3904","authenticated-orcid":false,"given":"Xin-Sheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3303-930X","authenticated-orcid":false,"given":"Hany M.","family":"Elsheikha","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2530-4628","authenticated-orcid":false,"given":"Xing-Quan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dubey, J.P. 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