{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:53:01Z","timestamp":1790243581616,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T00:00:00Z","timestamp":1522713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"David Winston Turner Foundation"},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI112962"],"award-info":[{"award-number":["AI112962"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI21423"],"award-info":[{"award-number":["AI21423"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["F31-AI120649"],"award-info":[{"award-number":["F31-AI120649"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000854","name":"Human Frontier Science Program","doi-asserted-by":"publisher","award":["LT000404\/2014-L"],"award-info":[{"award-number":["LT000404\/2014-L"]}],"id":[{"id":"10.13039\/501100000854","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Department of Education and Training | Australian Research Council","doi-asserted-by":"publisher","award":["FT120100164"],"award-info":[{"award-number":["FT120100164"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2018,5,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The obligate intracellular parasite\n            <jats:named-content content-type=\"genus-species\">Toxoplasma gondii<\/jats:named-content>\n            controls its host cell from within the parasitophorous vacuole (PV) by using a number of diverse effector proteins, a subset of which require the aspartyl protease 5 enzyme (ASP5) and\/or the recently discovered MYR1 protein to cross the PV membrane. To examine the impact these effectors have in the context of the entirety of the host response to\n            <jats:italic>Toxoplasma<\/jats:italic>\n            , we used RNA-Seq to analyze the transcriptome expression profiles of human foreskin fibroblasts infected with wild-type RH (RH-WT), RH\u0394\n            <jats:italic>myr1<\/jats:italic>\n            , and RH\u0394\n            <jats:italic>asp5<\/jats:italic>\n            tachyzoites. Interestingly, the majority of the differentially regulated genes responding to\n            <jats:italic>Toxoplasma<\/jats:italic>\n            infection are MYR1 dependent. A subset of MYR1 responses were ASP5 independent, and MYR1 function did not require ASP5 cleavage, suggesting the export of some effectors requires only MYR1. Gene set enrichment analysis of MYR1-dependent host responses suggests an upregulation of E2F transcription factors and the cell cycle and a downregulation related to interferon signaling, among numerous others. Most surprisingly, \u201chidden\u201d responses arising in RH\u0394\n            <jats:italic>myr1<\/jats:italic>\n            - but not RH-WT-infected host cells indicate counterbalancing actions of MYR1-dependent and -independent activities. The host genes and gene sets revealed here to be MYR1 dependent provide new insight into the parasite\u2019s ability to co-opt host cell functions.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content content-type=\"genus-species\">Toxoplasma gondii<\/jats:named-content>\n            is unique in its ability to successfully invade and replicate in a broad range of host species and cells within those hosts. The complex interplay of effector proteins exported by\n            <jats:italic>Toxoplasma<\/jats:italic>\n            is key to its success in co-opting the host cell to create a favorable replicative niche. Here we show that a majority of the transcriptomic effects in tachyzoite-infected cells depend on the activity of a novel translocation system involving MYR1 and that the effectors delivered by this system are part of an intricate interplay of activators and suppressors. Removal of all MYR1-dependent effectors reveals previously unknown activities that are masked or hidden by the action of these proteins.\n          <\/jats:p>","DOI":"10.1128\/mbio.02401-17","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T10:12:53Z","timestamp":1522663973000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":62,"title":["MYR1-Dependent Effectors Are the Major Drivers of a Host Cell\u2019s Early Response to\n            <i>Toxoplasma<\/i>\n            , Including Counteracting MYR1-Independent Effects"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4770-3099","authenticated-orcid":false,"given":"Adit","family":"Naor","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Panas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Coffey","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria, Australia"},{"name":"Department of Medical Biology, The University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7036-6222","authenticated-orcid":false,"given":"Christopher J.","family":"Tonkin","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria, Australia"},{"name":"Department of Medical Biology, The University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Boothroyd","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"114","article-title":"Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts","volume":"73","author":"Carruthers VB","year":"1997","unstructured":"Carruthers VB, Sibley LD. 1997. 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