{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:23:46Z","timestamp":1789982626293,"version":"4.0.1"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1004102","type":"journal-article","created":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T20:55:09Z","timestamp":1398977709000},"page":"e1004102","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":40,"title":["The Human Adenovirus E4-ORF1 Protein Subverts Discs Large 1 to Mediate Membrane Recruitment and Dysregulation of Phosphatidylinositol 3-Kinase"],"prefix":"10.1371","volume":"10","author":[{"given":"Kathleen","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Taruishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald T.","family":"Javier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"key":"ref1","unstructured":"Horwitz MS (2001) Adenoviruses. In: Knipe D, Howley P, editors. Fields Virology. Philadelphia: Lippincott, Williams and Wilkins. pp. 2301\u20132326."},{"key":"ref2","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1128\/JVI.65.6.3192-3202.1991","article-title":"Human adenovirus type 9-induced rat mammary tumors","volume":"65","author":"R Javier","year":"1991","journal-title":"Journal of Virology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1128\/JVI.68.6.3917-3924.1994","article-title":"Adenovirus type 9 E4 open reading frame 1 encodes a transforming protein required for the production of mammary tumors in rats","volume":"68","author":"RT Javier","year":"1994","journal-title":"Journal of Virology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1128\/JVI.70.2.862-872.1996","article-title":"Human adenovirus type 9 E4 open reading frame 1 encodes a cytoplasmic transforming protein capable of increasing the oncogenicity of CREF cells","volume":"70","author":"RS Weiss","year":"1996","journal-title":"Journal of Virology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1038\/sj.onc.1210784","article-title":"Functionally distinct monomers and trimers produced by a viral oncoprotein","volume":"27","author":"SH Chung","year":"2008","journal-title":"Oncogene"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1128\/JVI.71.3.1857-1870.1997","article-title":"Human adenovirus early region 4 open reading frame 1 genes encode growth-transforming proteins that may be distantly related to dUTP pyrophosphatase enzymes","volume":"71","author":"RS Weiss","year":"1997","journal-title":"Journal of Virology"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/sj.onc.1206151","article-title":"Selective PDZ protein-dependent stimulation of phosphatidylinositol 3-kinase by the adenovirus E4-ORF1 oncoprotein","volume":"22","author":"KK Frese","year":"2003","journal-title":"Oncogene"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/sj.emboj.7600597","article-title":"Adenoviral proteins mimic nutrient\/growth signals to activate the mTOR pathway for viral replication","volume":"24","author":"C O'Shea","year":"2005","journal-title":"EMBO J"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"883","DOI":"10.4161\/cc.4.7.1791","article-title":"Adenovirus overrides cellular checkpoints for protein translation","volume":"4","author":"CC O'Shea","year":"2005","journal-title":"Cell Cycle"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"19288","DOI":"10.1073\/pnas.0805980105","article-title":"Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene","volume":"105","author":"M Seandel","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"e47813","DOI":"10.1371\/journal.pone.0047813","article-title":"E4orf1 improves lipid and glucose metabolism in hepatocytes: a template to improve steatosis & hyperglycemia","volume":"7","author":"EJ Dhurandhar","year":"2012","journal-title":"PloS One"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrm2882","article-title":"The emerging mechanisms of isoform-specific PI3K signalling","volume":"11","author":"B Vanhaesebroeck","year":"2010","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"5497","DOI":"10.1038\/onc.2008.245","article-title":"PI3K pathway alterations in cancer: variations on a theme","volume":"27","author":"TL Yuan","year":"2008","journal-title":"Oncogene"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1099\/vir.0.19771-0","article-title":"The pivotal role of phosphatidylinositol 3-kinase-Akt signal transduction in virus survival","volume":"85","author":"S Cooray","year":"2004","journal-title":"The Journal of General Virology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"4787","DOI":"10.1128\/JVI.02855-06","article-title":"A New Crucial Protein-Interaction Element That Targets the Adenovirus E4-ORF1 Oncoprotein to Membrane Vesicles","volume":"81","author":"SH Chung","year":"2007","journal-title":"Journal of Virology"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1128\/JVI.75.2.557-568.2001","article-title":"Several E4 region functions influence mammary tumorigenesis by human adenovirus type 9","volume":"75","author":"DL Thomas","year":"2001","journal-title":"Journal of Virology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"4385","DOI":"10.1128\/JVI.71.6.4385-4394.1997","article-title":"Mutant adenovirus type 9 E4 ORF1 genes define three protein regions required for transformation of CREF cells","volume":"71","author":"RS Weiss","year":"1997","journal-title":"Journal of Virology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"7873","DOI":"10.1128\/JVI.71.10.7873-7880.1997","article-title":"A carboxy-terminal region required by the adenovirus type 9 E4 ORF1 oncoprotein for transformation mediates direct binding to cellular polypeptides","volume":"71","author":"RS Weiss","year":"1997","journal-title":"Journal of Virology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"6670","DOI":"10.1073\/pnas.94.13.6670","article-title":"Binding of human virus oncoproteins to hDlg\/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein","volume":"94","author":"SS Lee","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"11612","DOI":"10.1073\/pnas.94.21.11612","article-title":"Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein","volume":"94","author":"T Kiyono","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/sj.onc.1201567","article-title":"The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins","volume":"16","author":"R Rousset","year":"1998","journal-title":"Oncogene"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"7031","DOI":"10.1038\/onc.2008.352","article-title":"Cell polarity proteins: common targets for tumorigenic human viruses","volume":"27","author":"RT Javier","year":"2008","journal-title":"Oncogene"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"11544","DOI":"10.1128\/JVI.05410-11","article-title":"Emerging theme: cellular PDZ proteins as common targets of pathogenic viruses","volume":"85","author":"RT Javier","year":"2011","journal-title":"Journal of Virology"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"7018","DOI":"10.1038\/onc.2008.351","article-title":"Human papillomaviruses, cervical cancer and cell polarity","volume":"27","author":"M Thomas","year":"2008","journal-title":"Oncogene"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"5270","DOI":"10.1038\/sj.onc.1203906","article-title":"Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins","volume":"19","author":"BA Glaunsinger","year":"2000","journal-title":"Oncogene"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"5578","DOI":"10.1093\/emboj\/20.20.5578","article-title":"Link of the unique oncogenic properties of adenovirus type 9 E4-ORF1 to a select interaction with the candidate tumor suppressor protein ZO-2","volume":"20","author":"BA Glaunsinger","year":"2001","journal-title":"EMBO J"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"4283","DOI":"10.1242\/jcs.02560","article-title":"Viral oncoprotein-induced mislocalization of select PDZ proteins disrupts tight junctions and causes polarity defects in epithelial cells","volume":"118","author":"IJ Latorre","year":"2005","journal-title":"J Cell Sci"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"9680","DOI":"10.1128\/JVI.74.20.9680-9693.2000","article-title":"Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins","volume":"74","author":"SS Lee","year":"2000","journal-title":"Journal of Virology"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"413","DOI":"10.3109\/01913129809032276","article-title":"Altered gap and tight junctions in human thyroid oncocytic tumors: a study of 8 cases by freeze-fracture","volume":"22","author":"B Cochand-Priollet","year":"1998","journal-title":"Ultrastruct Pathol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1146\/annurev-cellbio-092910-154244","article-title":"Cell polarity as a regulator of cancer cell behavior plasticity","volume":"28","author":"SK Muthuswamy","year":"2012","journal-title":"Annual Review of Cell and Developmental Biology"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/carcin\/20.8.1425","article-title":"Increased tight junctional permeability is associated with the development of colon cancer","volume":"20","author":"AP Soler","year":"1999","journal-title":"Carcinogenesis"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"9818","DOI":"10.1073\/pnas.91.21.9818","article-title":"Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1","volume":"91","author":"RA Lue","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1111\/j.1742-4658.2012.08729.x","article-title":"The PDZ protein discs-large (DLG): the \u2018Jekyll and Hyde\u2019 of the epithelial polarity proteins","volume":"279","author":"S Roberts","year":"2012","journal-title":"The FEBS Journal"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1038\/sj.emboj.7601030","article-title":"Oncogenic function for the Dlg1 mammalian homolog of the Drosophila discs-large tumor suppressor","volume":"25","author":"KK Frese","year":"2006","journal-title":"EMBO J"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"e1002543","DOI":"10.1371\/journal.ppat.1002543","article-title":"The invasive capacity of HPV transformed cells requires the hDlg-dependent enhancement of SGEF\/RhoG activity","volume":"8","author":"V Krishna Subbaiah","year":"2012","journal-title":"PLoS Pathogens"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1083\/jcb.135.4.1125","article-title":"Two independent domains of hDlg are sufficient for subcellular targeting: the PDZ1-2 conformational unit and an alternatively spliced domain","volume":"135","author":"RA Lue","year":"1996","journal-title":"J Cell Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1083\/jcb.135.3.753","article-title":"Modular organization of the PDZ domains in the human discs-large protein suggests a mechanism for coupling PDZ domain-binding proteins to ATP and the membrane cytoskeleton","volume":"135","author":"SM Marfatia","year":"1996","journal-title":"J Cell Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nature11288","article-title":"Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins","volume":"487","author":"O Rozenblatt-Rosen","year":"2012","journal-title":"Nature"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S1046-2023(03)00032-X","article-title":"Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures","volume":"30","author":"J Debnath","year":"2003","journal-title":"Methods"},{"key":"ref40","unstructured":"Topp WC, Lane D, Pollack R (1981) Transformation by simian virus 40 and polyoma virus. In: Tooze J, editor. DNA Tumor Viruses. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory. pp. 205\u2013296."},{"key":"ref41","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.semcancer.2009.03.002","article-title":"Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens","volume":"19","author":"J Cheng","year":"2009","journal-title":"Seminars in Cancer Biology"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"e1003237","DOI":"10.1371\/journal.ppat.1003237","article-title":"The HPV16 E6 oncoprotein causes prolonged receptor protein tyrosine kinase signaling and enhances internalization of phosphorylated receptor species","volume":"9","author":"JM Spangle","year":"2013","journal-title":"PLoS Pathogens"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.virol.2011.12.018","article-title":"Cellular transformation by human papillomaviruses: lessons learned by comparing high- and low-risk viruses","volume":"424","author":"AJ Klingelhutz","year":"2012","journal-title":"Virology"},{"key":"ref44","first-page":"401","article-title":"AKTivation of PI3K\/AKT\/mTOR signaling pathway by KSHV","volume":"3","author":"AP Bhatt","year":"2012","journal-title":"Frontiers in Immunology"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1128\/JVI.02395-12","article-title":"Varicella-zoster virus ORF12 protein activates the phosphatidylinositol 3-kinase\/Akt pathway to regulate cell cycle progression","volume":"87","author":"X Liu","year":"2013","journal-title":"Journal of Virology"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1128\/JVI.01877-10","article-title":"Herpes simplex virus requires VP11\/12 to activate Src family kinase-phosphoinositide 3-kinase-Akt signaling","volume":"85","author":"MJ Wagner","year":"2011","journal-title":"Journal of Virology"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.2741\/1738","article-title":"The herpes simplex virus type 2 protein ICP10PK: a master of versatility","volume":"10","author":"CC Smith","year":"2005","journal-title":"Frontiers in bioscience"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"6677","DOI":"10.1128\/JVI.06860-11","article-title":"Integrin beta1 mediates vaccinia virus entry through activation of PI3K\/Akt signaling","volume":"86","author":"R Izmailyan","year":"2012","journal-title":"Journal of Virology"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"8927","DOI":"10.1074\/jbc.M510598200","article-title":"Role for Akt\/protein kinase B and activator protein-1 in cellular proliferation induced by the human T-cell leukemia virus type 1 tax oncoprotein","volume":"281","author":"JM Peloponese Jr","year":"2006","journal-title":"The Journal of Biological Chemistry"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1128\/JVI.02479-12","article-title":"Molecular mechanism behind rotavirus NSP1-mediated PI3 kinase activation: interaction between NSP1 and the p85 subunit of PI3 kinase","volume":"87","author":"P Bagchi","year":"2013","journal-title":"Journal of Virology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1111\/j.1462-5822.2009.01309.x","article-title":"A new player in a deadly game: influenza viruses and the PI3K\/Akt signalling pathway","volume":"11","author":"C Ehrhardt","year":"2009","journal-title":"Cellular Microbiology"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.jbior.2012.04.002","article-title":"PI3K keeps the balance between metabolism and cancer","volume":"52","author":"L Braccini","year":"2012","journal-title":"Advances in Biological Regulation"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s10549-007-9847-6","article-title":"Comprehensive analysis of oncogenic effects of PIK3CA mutations in human mammary epithelial cells","volume":"112","author":"H Zhang","year":"2008","journal-title":"Breast Cancer Research and Treatment"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"10157","DOI":"10.1074\/jbc.M309843200","article-title":"Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells","volume":"279","author":"P Laprise","year":"2004","journal-title":"The Journal of Biological Chemistry"},{"key":"ref55","first-page":"35","article-title":"Threonine phosphorylation of the MMAC1\/PTEN PDZ binding domain both inhibits and stimulates PDZ binding","volume":"60","author":"NB Adey","year":"2000","journal-title":"Cancer Research"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"28936","DOI":"10.1074\/jbc.M504761200","article-title":"Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine\/threonine kinases","volume":"280","author":"M Valiente","year":"2005","journal-title":"The Journal of Biological Chemistry"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1126\/science.1187735","article-title":"Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination","volume":"328","author":"L Cotter","year":"2010","journal-title":"Science"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1002\/jcb.24141","article-title":"A functional network of the tumor suppressors APC, hDlg, and PTEN, that relies on recognition of specific PDZ-domains","volume":"113","author":"NS Sotelo","year":"2012","journal-title":"Journal of Cellular Biochemistry"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.virol.2008.09.040","article-title":"E6 variants of human papillomavirus 18 differentially modulate the protein kinase B\/phosphatidylinositol 3-kinase (akt\/PI3K) signaling pathway","volume":"383","author":"A Contreras-Paredes","year":"2009","journal-title":"Virology"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"7466","DOI":"10.1128\/JVI.00487-12","article-title":"Activation of cap-dependent translation by mucosal human papillomavirus E6 proteins is dependent on the integrity of the LXXLL binding motif","volume":"86","author":"JM Spangle","year":"2012","journal-title":"Journal of Virology"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1038\/sj.onc.1204364","article-title":"Phosphoinositide-3 kinase-PKB\/Akt pathway activation is involved in fibroblast Rat-1 transformation by human T-cell leukemia virus type I tax","volume":"20","author":"Y Liu","year":"2001","journal-title":"Oncogene"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"6719","DOI":"10.1038\/sj.onc.1208825","article-title":"Activated AKT regulates NF-kappaB activation, p53 inhibition and cell survival in HTLV-1-transformed cells","volume":"24","author":"SJ Jeong","year":"2005","journal-title":"Oncogene"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.virol.2010.04.018","article-title":"Activation of the PI3K-Akt pathway by human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells","volume":"403","author":"K Saito","year":"2010","journal-title":"Virology"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1128\/JVI.00036-11","article-title":"The human T-cell leukemia virus type 1 oncoprotein tax controls forkhead box O4 activity through degradation by the proteasome","volume":"85","author":"A Oteiza","year":"2011","journal-title":"Journal of Virology"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1182\/blood-2009-08-241117","article-title":"HTLV-I Tax-dependent and -independent events associated with immortalization of human primary T lymphocytes","volume":"115","author":"M Bellon","year":"2010","journal-title":"Blood"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"4861","DOI":"10.1128\/JVI.02608-12","article-title":"Synergistic effect of the PDZ and p85beta-binding domains of the NS1 protein on virulence of an avian H5N1 influenza A virus","volume":"87","author":"S Fan","year":"2013","journal-title":"Journal of Virology"}],"container-title":["PLoS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1004102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T18:25:41Z","timestamp":1597775141000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1004102"}},"subtitle":[],"editor":[{"given":"Michael J.","family":"Imperiale","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,5,1]]},"references-count":66,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,5,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1004102","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,1]]}}}