{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:48:56Z","timestamp":1785422936437,"version":"3.56.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"DOI":"10.3389\/fcimb.2020.00488","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T04:51:58Z","timestamp":1599627118000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Infection by the Protozoan Parasite Toxoplasma gondii Inhibits Host MNK1\/2-eIF4E Axis to Promote Its Survival"],"prefix":"10.3389","volume":"10","author":[{"given":"Louis-Philippe","family":"Leroux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Visnu","family":"Chaparro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maritza","family":"Jaramillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1038\/s41467-018-04883-5","article-title":"Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E","volume":"9","author":"Aguilar-Valles","year":"2018","journal-title":"Nat. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1073\/pnas.0912344107","article-title":"Vesicular stomatitis virus oncolysis is potentiated by impairing mTORC1-dependent type I IFN production","volume":"107","author":"Alain","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2707","DOI":"10.1007\/s00436-017-5579-7","article-title":"Toxoplasma gondii and Neospora caninum induce different host cell responses at proteome-wide phosphorylation events; a step forward for uncovering the biological differences between these closely related parasites","volume":"116","author":"Al-Bajalan","year":"2017","journal-title":"Parasitol. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1523\/JNEUROSCI.2673-17.2018","article-title":"Loss of eIF4E phosphorylation engenders depression-like behaviors via selective mRNA translation","volume":"38","author":"Amorim","year":"2018","journal-title":"J. Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"F1000","DOI":"10.12688\/f1000research.16021.1","article-title":"Metabolic interactions between Toxoplasma gondii and its host","volume":"7","author":"Blume","year":"2018","journal-title":"F1000Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.chom.2013.03.002","article-title":"Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression","volume":"13","author":"Bougdour","year":"2013","journal-title":"Cell Host Microbe"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1084\/jem.20130103","article-title":"A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation","volume":"210","author":"Braun","year":"2013","journal-title":"J. Exp. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.immuni.2005.06.009","article-title":"The Mnks are novel components in the control of TNF alpha biosynthesis and phosphorylate and regulate hnRNP A1","volume":"23","author":"Buxade","year":"2005","journal-title":"Immunity"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e1008291","DOI":"10.1371\/journal.ppat.1008291","article-title":"Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts","volume":"16","author":"Chaparro","year":"2020","journal-title":"PLoS Pathog."},{"key":"B10","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.pt.2017.02.007","article-title":"The Toxoplasma parasitophorous vacuole: an evolving host-parasite frontier","volume":"33","author":"Clough","year":"2017","journal-title":"Trends Parasitol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3389\/fcimb.2019.00046","article-title":"From entry to early dissemination-Toxoplasma gondii's initial encounter with its host","volume":"9","author":"Delgado Betancourt","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1128\/CMR.11.4.569","article-title":"Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection","volume":"11","author":"Denkers","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"14134","DOI":"10.1073\/pnas.1005320107","article-title":"eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression","volume":"107","author":"Furic","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B14","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/nrm1488","article-title":"Molecular mechanisms of translational control","volume":"5","author":"Gebauer","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2852","DOI":"10.1101\/gad.912401","article-title":"Hierarchical phosphorylation of the translation inhibitor 4E-BP1","volume":"15","author":"Gingras","year":"2001","journal-title":"Genes Dev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1128\/CMR.00005-17","article-title":"Toxoplasma effectors targeting host signaling and transcription","volume":"30","author":"Hakimi","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e39887","DOI":"10.7554\/eLife.39887.027","article-title":"Characterization of a Toxoplasma effector uncovers an alternative GSK3\/beta-catenin-regulatory pathway of inflammation","volume":"7","author":"He","year":"2018","journal-title":"Elife"},{"key":"B18","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/ni.2291","article-title":"Translational control of the activation of transcription factor NF-kappaB and production of type I interferon by phosphorylation of the translation factor eIF4E","volume":"13","author":"Herdy","year":"2012","journal-title":"Nat. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"a011528","DOI":"10.1101\/cshperspect.a011528","article-title":"Principles of translational control: an overview","volume":"4","author":"Hershey","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4010","DOI":"10.1016\/j.celrep.2019.11.072","article-title":"Induction of an alternative mRNA 5\u2032 leader enhances translation of the ciliopathy gene Inpp5e and resistance to oncolytic virus infection","volume":"29","author":"Hoang","year":"2019","journal-title":"Cell Rep."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e00053","DOI":"10.1016\/j.fawpar.2019.e00053","article-title":"A one health approach to vaccines against Toxoplasma gondii","volume":"15","author":"Innes","year":"2019","journal-title":"Food Waterborne Parasitol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/nrm2838","article-title":"The mechanism of eukaryotic translation initiation and principles of its regulation","volume":"11","author":"Jackson","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2584","DOI":"10.4049\/jimmunol.177.4.2584","article-title":"Toxoplasma gondii genotype determines MyD88-dependent signaling in infected macrophages","volume":"177","author":"Kim","year":"2006","journal-title":"J. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1006\/viro.1996.0143","article-title":"Phosphorylation state of the cap-binding protein eIF4E during viral infection","volume":"217","author":"Kleijn","year":"1996","journal-title":"Virology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3455","DOI":"10.1074\/jbc.M115.694190","article-title":"Inhibition of mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) preferentially affects translation of mRNAs containing both a 5\u2032-terminal cap and hairpin","volume":"291","author":"Korneeva","year":"2016","journal-title":"J. Biol. Chem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.ijpara.2015.01.003","article-title":"Secreted Toxoplasma gondii molecules interfere with expression of MHC-II in interferon gamma-activated macrophages","volume":"45","author":"Leroux","year":"","journal-title":"Int. J. Parasitol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e00244","DOI":"10.1128\/IAI.00244-18","article-title":"The protozoan parasite Toxoplasma gondii selectively reprograms the host cell translatome","volume":"86","author":"Leroux","year":"2018","journal-title":"Infect. Immun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3865","DOI":"10.1128\/IAI.00415-15","article-title":"Parasite manipulation of the invariant chain and the peptide editor H2-DM affects major histocompatibility complex class II antigen presentation during Toxoplasma gondii infection","volume":"83","author":"Leroux","year":"","journal-title":"Infect. Immun."},{"key":"B29","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1593\/neo.10704","article-title":"Protein phosphatase 2A negatively regulates eukaryotic initiation factor 4E phosphorylation and eIF4F assembly through direct dephosphorylation of Mnk and eIF4E","volume":"12","author":"Li","year":"2010","journal-title":"Neoplasia"},{"key":"B30","doi-asserted-by":"publisher","first-page":"30199","DOI":"10.1074\/jbc.271.47.30199","article-title":"Control of the translational regulators PHAS-I and PHAS-II by insulin and cAMP in 3T3-L1 adipocytes","volume":"271","author":"Lin","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B32","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1093\/clinids\/15.2.211","article-title":"Toxoplasmic encephalitis in AIDS","volume":"15","author":"Luft","year":"1992","journal-title":"Clin. Infect. Dis."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-020-00220-1","article-title":"eIF4E phosphorylation modulates pain and neuroinflammation in the aged","author":"Mody","year":"2020","journal-title":"Geroscience"},{"key":"B34","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.chom.2012.09.006","article-title":"Host translation at the nexus of infection and immunity","volume":"12","author":"Mohr","year":"2012","journal-title":"Cell Host Microbe"},{"key":"B35","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fmicb.2017.00025","article-title":"A systematic review of in vitro and in vivo activities of anti-Toxoplasma drugs and compounds (2006-2016)","volume":"8","author":"Montazeri","year":"2017","journal-title":"Front. Microbiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1086\/590149","article-title":"Management of Toxoplasma gondii infection during pregnancy","volume":"47","author":"Montoya","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e114854","DOI":"10.1371\/journal.pone.0114854","article-title":"Deficiency in either 4E-BP1 or 4E-BP2 augments innate antiviral immune responses","volume":"9","author":"Nehdi","year":"2014","journal-title":"PLoS ONE"},{"key":"B38","doi-asserted-by":"publisher","first-page":"jcs.241752","DOI":"10.1242\/jcs.241752","article-title":"Convergent Met and voltage-gated Ca(2+) channel signaling drives hypermigration of Toxoplasma-infected dendritic cells","volume":"134","author":"Olafsson","year":"2020","journal-title":"J. Cell Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1038\/371762a0","article-title":"Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5\u2032-cap function","volume":"371","author":"Pause","year":"1994","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1158\/0008-5472.CAN-14-2789","article-title":"Targeting the eIF4F translation initiation complex: a critical nexus for cancer development","volume":"75","author":"Pelletier","year":"2015","journal-title":"Cancer Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/ni.2891","article-title":"Translational control of immune responses: from transcripts to translatomes","volume":"15","author":"Piccirillo","year":"2014","journal-title":"Nat. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.bbagrm.2014.10.003","article-title":"Mnks, eIF4E phosphorylation and cancer","volume":"1849","author":"Proud","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1038\/onc.2014.146","article-title":"Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3","volume":"34","author":"Robichaud","year":"2015","journal-title":"Oncogene"},{"key":"B44","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.chom.2019.09.008","article-title":"In vivo CRISPR screen identifies TgWIP as a Toxoplasma modulator of dendritic cell migration","volume":"26","author":"Sangare","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B45","doi-asserted-by":"publisher","first-page":"5350","DOI":"10.1046\/j.1432-1033.2002.03291.x","article-title":"Does phosphorylation of the cap-binding protein eIF4E play a role in translation initiation?","volume":"269","author":"Scheper","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3303","DOI":"10.1074\/jbc.M103607200","article-title":"Phosphorylation of eukaryotic initiation factor 4E markedly reduces its affinity for capped mRNA","volume":"277","author":"Scheper","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"14927","DOI":"10.1074\/jbc.M601653200","article-title":"Stopped-flow kinetic analysis of eIF4E and phosphorylated eIF4E binding to cap analogs and capped oligoribonucleotides: evidence for a one-step binding mechanism","volume":"281","author":"Slepenkov","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B48","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.cell.2009.01.042","article-title":"Regulation of translation initiation in eukaryotes: mechanisms and biological targets","volume":"136","author":"Sonenberg","year":"2009","journal-title":"Cell"},{"key":"B49","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1038\/ni.3205","article-title":"Interferon-gamma regulates cellular metabolism and mRNA translation to potentiate macrophage activation","volume":"16","author":"Su","year":"2015","journal-title":"Nat. Immunol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"6539","DOI":"10.1128\/MCB.24.15.6539-6549.2004","article-title":"Mnk2 and Mnk1 are essential for constitutive and inducible phosphorylation of eukaryotic initiation factor 4E but not for cell growth or development","volume":"24","author":"Ueda","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"525","DOI":"10.2174\/1389203720666190110142438","article-title":"Biochemical and structural insights into the eukaryotic translation initiation factor eIF4E","volume":"20","author":"Volpon","year":"2019","journal-title":"Curr. Prot. Pept. Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"a012351","DOI":"10.1101\/cshperspect.a012351","article-title":"Tinkering with translation: protein synthesis in virus-infected cells","volume":"5","author":"Walsh","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1101\/gad.1185304","article-title":"Phosphorylation of eIF4E by Mnk-1 enhances HSV-1 translation and replication in quiescent cells","volume":"18","author":"Walsh","year":"2004","journal-title":"Genes Dev."},{"key":"B54","doi-asserted-by":"publisher","first-page":"15611","DOI":"10.1074\/jbc.M109.095778","article-title":"Coordinate control of host centrosome position, organelle distribution, and migratory response by Toxoplasma gondii via host mTORC2","volume":"285","author":"Wang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1093\/emboj\/16.8.1909","article-title":"Mitogen-activated protein kinases activate the serine\/threonine kinases Mnk1 and Mnk2","volume":"16","author":"Waskiewicz","year":"1997","journal-title":"EMBO J."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1002\/eji.201847857","article-title":"Translational repression of Ccl5 and Cxcl10 by 4E-BP1 and 4E-BP2 restrains the ability of mouse macrophages to induce migration of activated T cells","volume":"49","author":"William","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1080\/14728222.2019.1571043","article-title":"The MAP kinase-interacting kinases (MNKs) as targets in oncology","volume":"23","author":"Xie","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"B58","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/ni.2304","article-title":"Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization","volume":"13","author":"Xu","year":"2012","journal-title":"Nat. Immunol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/mmi.13715","article-title":"The serine\/threonine phosphatases of apicomplexan parasites","volume":"106","author":"Yang","year":"2017","journal-title":"Mol. Microbiol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1074\/mcp.M116.063602","article-title":"A human proteome array approach to identifying key host proteins targeted by Toxoplasma kinase ROP18","volume":"16","author":"Yang","year":"2017","journal-title":"Mol. Cell. Proteomics"},{"key":"B61","doi-asserted-by":"publisher","first-page":"e1007264","DOI":"10.1371\/journal.ppat.1007264","article-title":"Active-site mTOR inhibitors augment HSV1-dICP0 infection in cancer cells via dysregulated eIF4E\/4E-BP axis","volume":"14","author":"Zakaria","year":"2018","journal-title":"PLoS Pathog."},{"key":"B62","doi-asserted-by":"publisher","first-page":"5370","DOI":"10.1021\/bi030266t","article-title":"Influence of electric charge variation at residues 209 and 159 on the interaction of eIF4E with the mRNA 5\u2032 terminus","volume":"43","author":"Zuberek","year":"2004","journal-title":"Biochemistry"},{"key":"B63","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1261\/rna.2133403","article-title":"Phosphorylation of eIF4E attenuates its interaction with mRNA 5\u2032 cap analogs by electrostatic repulsion: intein-mediated protein ligation strategy to obtain phosphorylated protein","volume":"9","author":"Zuberek","year":"2003","journal-title":"RNA"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2020.00488\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T04:52:00Z","timestamp":1599627120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2020.00488\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,9]]},"references-count":63,"alternative-id":["10.3389\/fcimb.2020.00488"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2020.00488","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,9]]},"article-number":"488"}}