{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:06:36Z","timestamp":1790539596747,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T00:00:00Z","timestamp":1578268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31802180"],"award-info":[{"award-number":["31802180"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009620","name":"Gansu Science and Technology Department","doi-asserted-by":"publisher","award":["17JR7WA031"],"award-info":[{"award-number":["17JR7WA031"]}],"id":[{"id":"10.13039\/501100009620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005196","name":"Chinese Academy of Agricultural Sciences","doi-asserted-by":"publisher","award":["CAAS\u2010ASTIP\u20102016\u2010LVRI\u201003"],"award-info":[{"award-number":["CAAS\u2010ASTIP\u20102016\u2010LVRI\u201003"]}],"id":[{"id":"10.13039\/501100005196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dense granule protein 12 (GRA12) is implicated in a range of processes related to the establishment of\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    infection, such as the formation of the intravacuolar network (IVN) within the parasitophorous vacuole (PV). This protein is also\u00a0thought to be important for\n                    <jats:italic>T. gondii<\/jats:italic>\n                    \u2010host interaction, pathogenesis, and immune evasion, but their exact roles remain unknown. In this study, the contributions of GRA12 to the molecular pathogenesis of\n                    <jats:italic>T. gondii<\/jats:italic>\n                    infection were examined in vitro and in vivo. Deletion of GRA12 in type I RH and type II Pru\n                    <jats:italic>T. gondii<\/jats:italic>\n                    strains did not affect the parasite growth and replication in vitro\n                    <jats:italic>,<\/jats:italic>\n                    however,\u00a0it caused a significant reduction in the parasite virulence and tissue cyst burden in vivo.\n                    <jats:italic>T. gondii<\/jats:italic>\n                    \u0394\n                    <jats:italic>gra12<\/jats:italic>\n                    mutants were more vulnerable to be eliminated by host immunity, without the accumulation of immunity\u2010related GTPase a6 (Irga6) onto the PV membrane. The ultrastructure of IVN in \u0394\n                    <jats:italic>gra12<\/jats:italic>\n                    mutants appeared normal, suggesting that GRA12 is not required for biogenesis of the IVN. Combined deletion of GRA12 and ROP18 induced more severe attenuation of virulence compared to single \u0394\n                    <jats:italic>gra12<\/jats:italic>\n                    or \u0394\n                    <jats:italic>rop18<\/jats:italic>\n                    mutant strains. These data suggest a functional association between GRA12 and ROP18 that is revealed by the severe attenuation of virulence in a double mutant relative to the single individual mutations. Future studies are needed to define the molecular basis of this putative association. Collectively these findings indicate that although GRA12 is not essential for the parasite growth and replication in vitro, it contributes to the virulence and growth of\n                    <jats:italic>T. gondii<\/jats:italic>\n                    in mice.\n                  <\/jats:p>","DOI":"10.1096\/fj.201901416rr","type":"journal-article","created":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T01:51:40Z","timestamp":1578361900000},"page":"3165-3178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Novel roles of dense granule protein 12 (GRA12) in\n                    <i>Toxoplasma gondii<\/i>\n                    infection"],"prefix":"10.1096","volume":"34","author":[{"given":"Jin\u2010Lei","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology Key Laboratory of Veterinary Parasitology of Gansu Province Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences Lanzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Jie","family":"Bai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology Key Laboratory of Veterinary Parasitology of Gansu Province Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences Lanzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin\u2010Li","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology Key Laboratory of Veterinary Parasitology of Gansu Province Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences Lanzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Ting","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology Key Laboratory of Veterinary Parasitology of Gansu Province Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences Lanzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue\u2010Zhen","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine South China Agricultural University Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing\u2010Quan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology Key Laboratory of Veterinary Parasitology of Gansu Province Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences Lanzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16412-X"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.05013-11"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-091014-104353"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2858"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00005-17"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2015.04.003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003296"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.07.004"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-091014-104100"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.13018"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2017.02.007"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2014.12.002"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.2.509"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.06.009"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.10.021"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.07.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001358"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1133690"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1133643"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313501111"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.04.002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12499"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.39887"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.20182"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.108.4.1669"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E02-01-0021"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00297-10"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.9.4176-4182.1998"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2007.10.010"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm981"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00300"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2008.07.011"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-015-4791-6"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01114-14"},{"key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"e00754","DOI":"10.1128\/mBio.00754-16","article-title":"Not a simple tether: binding of Toxoplasma gondii AMA1 to RON2 during invasion protects AMA1 from rhomboid\u2010mediated cleavage and leads to dephosphorylation of its cytosolic tail","volume":"7","author":"Krishnamurthy S","year":"2016","journal-title":"MBio"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(97)00087-X"},{"key":"e_1_2_9_38_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3389\/fcimb.2019.00321","article-title":"The GRA17 parasitophorous vacuole membrane permeability pore contributes to bradyzoite viability","volume":"9","author":"Paredes\u2010Santos T","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099744"},{"key":"e_1_2_9_40_1","first-page":"84","article-title":"Functional characterization of rhoptry kinome in the virulent Toxoplasma gondii RH strain","volume":"8","author":"Wang JL","year":"2017","journal-title":"Front Microbiol"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12794"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01862-06"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy211"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0159306"},{"key":"e_1_2_9_45_1","first-page":"319","article-title":"Identification of novel dense\u2010granule proteins in Toxoplasma gondii by two proximity\u2010based biotinylation approaches","volume":"18","author":"Pan M","year":"2019","journal-title":"J Proteome Res"},{"key":"e_1_2_9_46_1","doi-asserted-by":"crossref","first-page":"e00808\u201316","DOI":"10.1128\/mBio.00808-16","article-title":"In vivo biotinylation of the Toxoplasma parasitophorous vacuole reveals novel dense granule proteins important for parasite growth and pathogenesis","volume":"7","author":"Nadipuram SM","year":"2016","journal-title":"MBio"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.04.003"},{"key":"e_1_2_9_48_1","doi-asserted-by":"crossref","first-page":"e00469\u201319","DOI":"10.1128\/mBio.00469-19","article-title":"Enrichment and proteomic characterization of the cyst wall from in vitro \n                  Toxoplasma gondii cysts","volume":"10","author":"Tu V","year":"2019","journal-title":"MBio"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e12-11-0827"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01188-14"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.11.001"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2004.07.011"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(99)00092-4"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816161116"},{"key":"e_1_2_9_55_1","article-title":"Toxoplasma gondii parasitophorous vacuole membrane\u2010associated dense granule proteins orchestrate chronic infection and GRA12 underpins resistance to host gamma interferon","volume":"10","author":"Fox BA","year":"2019","journal-title":"MBio"},{"key":"e_1_2_9_56_1","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1038\/s41467-019-11855-w","article-title":"A CRISPR platform for targeted in vivo screens identifies Toxoplasma gondii virulence factors in mice","volume":"10","author":"Young J","year":"2019","journal-title":"Nat Commun"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1096%2Ffj.201901416RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201901416RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201901416RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201901416RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:57:29Z","timestamp":1761674249000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201901416RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,6]]},"references-count":55,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1096\/fj.201901416RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.201901416rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,6]]},"assertion":[{"value":"2019-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}