{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:31:09Z","timestamp":1779114669207,"version":"3.51.4"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011264","name":"EC|FP7|FP7 People: Marie\u2010Curie Actions","doi-asserted-by":"publisher","award":["PCIG12\u2010GA\u20102012\u2010334081, X\u2010talk"],"award-info":[{"award-number":["PCIG12\u2010GA\u20102012\u2010334081, X\u2010talk"]}],"id":[{"id":"10.13039\/100011264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012654","name":"Olga Mayenfisch Stiftung","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012654","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008481","name":"Kurt und Senta Herrmann\u2010Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008481","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020 \u2010 Research and Innovation Framework Program","doi-asserted-by":"publisher","award":["777995, DISCOVER"],"award-info":[{"award-number":["777995, DISCOVER"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"name":"A generous donor advised by CARIGEST SA"},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_138188"],"award-info":[{"award-number":["310030_138188"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["314730_163086"],"award-info":[{"award-number":["314730_163086"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008494","name":"Vontobel Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008494","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007282","name":"Bern University Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007282","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Rep"],"published-print":{"date-parts":[[2020,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The role of death receptor signaling for pathogen control and infection\u2010associated pathogenesis is multifaceted and controversial. Here, we show that during viral infection, tumor necrosis factor\u2010related apoptosis\u2010inducing ligand (TRAIL) modulates NK cell activity independently of its pro\u2010apoptotic function. In mice infected with lymphocytic choriomeningitis virus (LCMV),\n                    <jats:italic>Trail<\/jats:italic>\n                    deficiency led to improved specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell responses, resulting in faster pathogen clearance and reduced liver pathology. Depletion experiments indicated that this effect was mediated by NK cells. Mechanistically, TRAIL expressed by immune cells positively and dose\u2010dependently modulates IL\u201015 signaling\u2010induced granzyme B production in NK cells, leading to enhanced NK cell\u2010mediated T cell killing. TRAIL also regulates the signaling downstream of IL\u201015 receptor in human NK cells. In addition, TRAIL restricts NK1.1\u2010triggered IFN\u03b3 production by NK cells. Our study reveals a hitherto unappreciated immunoregulatory role of TRAIL signaling on NK cells for the granzyme B\u2010dependent elimination of antiviral T cells.\n                  <\/jats:p>","DOI":"10.15252\/embr.201948789","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T11:11:35Z","timestamp":1576840295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Non\u2010apoptotic TRAIL function modulates NK cell activity during viral infection"],"prefix":"10.1038","volume":"21","author":[{"given":"Ludmila","family":"Cardoso Alves","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D","family":"Berger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thodoris","family":"Koutsandreas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick","family":"Kirschke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Lauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Sp\u00f6rri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2078-0844","authenticated-orcid":false,"given":"Aristotelis","family":"Chatziioannou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Corazza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4918-6654","authenticated-orcid":false,"given":"Philippe","family":"Krebs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"BFEMBR201948789_CR1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/nri3839","volume":"15","author":"I Voskoboinik","year":"2015","unstructured":"Voskoboinik I, Whisstock JC, Trapani JA (2015) Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol 15: 388\u2013400","journal-title":"Nat Rev Immunol"},{"key":"BFEMBR201948789_CR2","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.4049\/jimmunol.181.7.4918","volume":"181","author":"EL Brincks","year":"2008","unstructured":"Brincks EL, Katewa A, Kucaba TA, Griffith TS, Legge KL (2008) CD8 T cells utilize TRAIL to control influenza virus infection. J Immunol 181: 4918\u20134925","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR3","doi-asserted-by":"crossref","first-page":"7658","DOI":"10.1128\/JVI.79.12.7658-7663.2005","volume":"79","author":"E Ishikawa","year":"2005","unstructured":"Ishikawa E, Nakazawa M, Yoshinari M, Minami M (2005) Role of tumor necrosis factor\u2010related apoptosis\u2010inducing ligand in immune response to influenza virus infection in mice. J Virol 79: 7658\u20137663","journal-title":"J Virol"},{"key":"BFEMBR201948789_CR4","doi-asserted-by":"crossref","first-page":"a008698","DOI":"10.1101\/cshperspect.a008698","volume":"5","author":"H Walczak","year":"2013","unstructured":"Walczak H (2013) Death receptor\u2010ligand systems in cancer, cell death, and inflammation. Cold Spring Harb Perspect Biol 5: a008698","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"BFEMBR201948789_CR5","doi-asserted-by":"crossref","first-page":"E316","DOI":"10.3390\/v9110316","volume":"9","author":"X Zhou","year":"2017","unstructured":"Zhou X, Jiang W, Liu Z, Liu S, Liang X (2017) Virus infection and death receptor\u2010mediated apoptosis. Viruses 9: E316","journal-title":"Viruses"},{"key":"BFEMBR201948789_CR6","doi-asserted-by":"crossref","first-page":"495","DOI":"10.2174\/156652409788167078","volume":"9","author":"N Cummins","year":"2009","unstructured":"Cummins N, Badley A (2009) The TRAIL to viral pathogenesis: the good, the bad and the ugly. Curr Mol Med 9: 495\u2013505","journal-title":"Curr Mol Med"},{"key":"BFEMBR201948789_CR7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1089\/jir.2010.0026","volume":"30","author":"S Salek\u2010Ardakani","year":"2010","unstructured":"Salek\u2010Ardakani S, Croft M (2010) Tumor necrosis factor receptor\/tumor necrosis factor family members in antiviral CD8 T\u2010cell immunity. J Interferon Cytokine Res 30: 205\u2013218","journal-title":"J Interferon Cytokine Res"},{"key":"BFEMBR201948789_CR8","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1002\/1521-4141(200111)31:11<3138::AID-IMMU3138>3.0.CO;2-B","volume":"31","author":"K Sato","year":"2001","unstructured":"Sato K, Hida S, Takayanagi H, Yokochi T, Kayagaki N, Takeda K, Yagita H, Okumura K, Tanaka N, Taniguchi T et\u00a0al (2001) Antiviral response by natural killer cells through TRAIL gene induction by IFN\u2010alpha\/beta. Eur J Immunol 31: 3138\u20133146","journal-title":"Eur J Immunol"},{"key":"BFEMBR201948789_CR9","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1172\/JCI200419255","volume":"113","author":"SJ Zheng","year":"2004","unstructured":"Zheng SJ, Wang P, Tsabary G, Chen YH (2004) Critical roles of TRAIL in hepatic cell death and hepatic inflammation. J Clin Invest 113: 58\u201364","journal-title":"J Clin Invest"},{"key":"BFEMBR201948789_CR10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1084\/jem.20121172","volume":"210","author":"D Peppa","year":"2013","unstructured":"Peppa D, Gill US, Reynolds G, Easom NJ, Pallett LJ, Schurich A, Micco L, Nebbia G, Singh HD, Adams DH et\u00a0al (2013) Up\u2010regulation of a death receptor renders antiviral T cells susceptible to NK cell\u2010mediated deletion. J Exp Med 210: 99\u2013114","journal-title":"J Exp Med"},{"key":"BFEMBR201948789_CR11","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.immuni.2014.09.013","volume":"41","author":"IS Schuster","year":"2014","unstructured":"Schuster IS, Wikstrom ME, Brizard G, Coudert JD, Estcourt MJ, Manzur M, O'Reilly LA, Smyth MJ, Trapani JA, Hill GR et\u00a0al (2014) TRAIL+ NK cells control CD4+ T cell responses during chronic viral infection to limit autoimmunity. Immunity 41: 646\u2013656","journal-title":"Immunity"},{"key":"BFEMBR201948789_CR12","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/ni894","volume":"4","author":"SE Lamhamedi\u2010Cherradi","year":"2003","unstructured":"Lamhamedi\u2010Cherradi SE, Zheng SJ, Maguschak KA, Peschon J, Chen YH (2003) Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL\u2212\/\u2212 mice. Nat Immunol 4: 255\u2013260","journal-title":"Nat Immunol"},{"key":"BFEMBR201948789_CR13","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1084\/jem.191.7.1095","volume":"191","author":"K Song","year":"2000","unstructured":"Song K, Chen Y, Goke R, Wilmen A, Seidel C, Goke A, Hilliard B, Chen Y (2000) Tumor necrosis factor\u2010related apoptosis\u2010inducing ligand (TRAIL) is an inhibitor of autoimmune inflammation and cell cycle progression. J Exp Med 191: 1095\u20131104","journal-title":"J Exp Med"},{"key":"BFEMBR201948789_CR14","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/cdd.2013.28","volume":"20","author":"K Azijli","year":"2013","unstructured":"Azijli K, Weyhenmeyer B, Peters GJ, de Jong S, Kruyt FA (2013) Non\u2010canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family. Cell Death Differ 20: 858\u2013868","journal-title":"Cell Death Differ"},{"key":"BFEMBR201948789_CR15","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1038\/sj.onc.1206520","volume":"22","author":"H Ehrhardt","year":"2003","unstructured":"Ehrhardt H, Fulda S, Schmid I, Hiscott J, Debatin KM, Jeremias I (2003) TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL\u2010induced apoptosis mediated by NF\u2010kappaB. Oncogene 22: 3842\u20133852","journal-title":"Oncogene"},{"key":"BFEMBR201948789_CR16","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.ccell.2015.02.014","volume":"27","author":"S von Karstedt","year":"2015","unstructured":"von Karstedt S, Conti A, Nobis M, Montinaro A, Hartwig T, Lemke J, Legler K, Annewanter F, Campbell AD, Taraborrelli L et\u00a0al (2015) Cancer cell\u2010autonomous TRAIL\u2010R signaling promotes KRAS\u2010driven cancer progression, invasion, and metastasis. Cancer Cell 27: 561\u2013573","journal-title":"Cancer Cell"},{"key":"BFEMBR201948789_CR17","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1084\/jem.174.6.1425","volume":"174","author":"WP Fung\u2010Leung","year":"1991","unstructured":"Fung\u2010Leung WP, Kundig TM, Zinkernagel RM, Mak TW (1991) Immune response against lymphocytic choriomeningitis virus infection in mice without CD8 expression. J Exp Med 174: 1425\u20131429","journal-title":"J Exp Med"},{"key":"BFEMBR201948789_CR18","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3389\/fimmu.2016.00251","volume":"7","author":"K Pallmer","year":"2016","unstructured":"Pallmer K, Oxenius A (2016) Recognition and regulation of T cells by NK cells. Front Immunol 7: 251","journal-title":"Front Immunol"},{"key":"BFEMBR201948789_CR19","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nature10624","volume":"481","author":"SN Waggoner","year":"2011","unstructured":"Waggoner SN, Cornberg M, Selin LK, Welsh RM (2011) Natural killer cells act as rheostats modulating antiviral T cells. Nature 481: 394\u2013398","journal-title":"Nature"},{"key":"BFEMBR201948789_CR20","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1073\/pnas.1118834109","volume":"109","author":"PA Lang","year":"2012","unstructured":"Lang PA, Lang KS, Xu HC, Grusdat M, Parish IA, Recher M, Elford AR, Dhanji S, Shaabani N, Tran CW et\u00a0al (2012) Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T\u2010cell immunity. Proc Natl Acad Sci USA 109: 1210\u20131215","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR201948789_CR21","doi-asserted-by":"crossref","first-page":"641","DOI":"10.4049\/jimmunol.1202448","volume":"190","author":"KD Cook","year":"2013","unstructured":"Cook KD, Whitmire JK (2013) The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection. J Immunol 190: 641\u2013649","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR22","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1084\/jem.20010938","volume":"195","author":"F Gerosa","year":"2002","unstructured":"Gerosa F, Baldani\u2010Guerra B, Nisii C, Marchesini V, Carra G, Trinchieri G (2002) Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med 195: 327\u2013333","journal-title":"J Exp Med"},{"key":"BFEMBR201948789_CR23","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S1074-7613(03)00264-4","volume":"19","author":"R Mocikat","year":"2003","unstructured":"Mocikat R, Braumuller H, Gumy A, Egeter O, Ziegler H, Reusch U, Bubeck A, Louis J, Mailhammer R, Riethmuller G et\u00a0al (2003) Natural killer cells activated by MHC class I(low) targets prime dendritic cells to induce protective CD8 T cell responses. Immunity 19: 561\u2013569","journal-title":"Immunity"},{"key":"BFEMBR201948789_CR24","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/ni1138","volume":"5","author":"A Martin\u2010Fontecha","year":"2004","unstructured":"Martin\u2010Fontecha A, Thomsen LL, Brett S, Gerard C, Lipp M, Lanzavecchia A, Sallusto F (2004) Induced recruitment of NK cells to lymph nodes provides IFN\u2010gamma for T(H)1 priming. Nat Immunol 5: 1260\u20131265","journal-title":"Nat Immunol"},{"key":"BFEMBR201948789_CR25","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1002\/eji.200636290","volume":"36","author":"B Morandi","year":"2006","unstructured":"Morandi B, Bougras G, Muller WA, Ferlazzo G, Munz C (2006) NK cells of human secondary lymphoid tissues enhance T cell polarization via IFN\u2010gamma secretion. Eur J Immunol 36: 2394\u20132400","journal-title":"Eur J Immunol"},{"key":"BFEMBR201948789_CR26","doi-asserted-by":"crossref","first-page":"6593","DOI":"10.1182\/blood-2009-01-201467","volume":"113","author":"P Krebs","year":"2009","unstructured":"Krebs P, Barnes MJ, Lampe K, Whitley K, Bahjat KS, Beutler B, Janssen E, Hoebe K (2009) NK\u2010cell\u2010mediated killing of target cells triggers robust antigen\u2010specific T\u2010cell\u2010mediated and humoral responses. Blood 113: 6593\u20136602","journal-title":"Blood"},{"key":"BFEMBR201948789_CR27","doi-asserted-by":"crossref","first-page":"3572","DOI":"10.4049\/jimmunol.170.7.3572","volume":"170","author":"BA Rabinovich","year":"2003","unstructured":"Rabinovich BA, Li J, Shannon J, Hurren R, Chalupny J, Cosman D, Miller RG (2003) Activated, but not resting, T cells can be recognized and killed by syngeneic NK cells. J Immunol 170: 3572\u20133576","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR28","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.4049\/jimmunol.163.4.1906","volume":"163","author":"N Kayagaki","year":"1999","unstructured":"Kayagaki N, Yamaguchi N, Nakayama M, Takeda K, Akiba H, Tsutsui H, Okamura H, Nakanishi K, Okumura K, Yagita H (1999) Expression and function of TNF\u2010related apoptosis\u2010inducing ligand on murine activated NK cells. J Immunol 163: 1906\u20131913","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR29","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.immuni.2014.05.003","volume":"40","author":"J Crouse","year":"2014","unstructured":"Crouse J, Bedenikovic G, Wiesel M, Ibberson M, Xenarios I, Von Laer D, Kalinke U, Vivier E, Jonjic S, Oxenius A (2014) Type I interferons protect T cells against NK cell attack mediated by the activating receptor NCR1. Immunity 40: 961\u2013973","journal-title":"Immunity"},{"key":"BFEMBR201948789_CR30","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.immuni.2014.05.004","volume":"40","author":"HC Xu","year":"2014","unstructured":"Xu HC, Grusdat M, Pandyra AA, Polz R, Huang J, Sharma P, Deenen R, Kohrer K, Rahbar R, Diefenbach A et\u00a0al (2014) Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity. Immunity 40: 949\u2013960","journal-title":"Immunity"},{"key":"BFEMBR201948789_CR31","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3389\/fimmu.2016.00241","volume":"7","author":"F Simonetta","year":"2016","unstructured":"Simonetta F, Pradier A, Roosnek E (2016) T\u2010bet and eomesodermin in NK cell development, maturation, and function. Front Immunol 7: 241","journal-title":"Front Immunol"},{"key":"BFEMBR201948789_CR32","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.immuni.2007.04.010","volume":"26","author":"TA Fehniger","year":"2007","unstructured":"Fehniger TA, Cai SF, Cao X, Bredemeyer AJ, Presti RM, French AR, Ley TJ (2007) Acquisition of murine NK cell cytotoxicity requires the translation of a pre\u2010existing pool of granzyme B and perforin mRNAs. Immunity 26: 798\u2013811","journal-title":"Immunity"},{"key":"BFEMBR201948789_CR33","doi-asserted-by":"crossref","first-page":"5488","DOI":"10.1182\/blood-2008-10-187179","volume":"113","author":"L Chiossone","year":"2009","unstructured":"Chiossone L, Chaix J, Fuseri N, Roth C, Vivier E, Walzer T (2009) Maturation of mouse NK cells is a 4\u2010stage developmental program. Blood 113: 5488\u20135496","journal-title":"Blood"},{"key":"BFEMBR201948789_CR34","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3389\/fimmu.2014.00187","volume":"5","author":"N Nandagopal","year":"2014","unstructured":"Nandagopal N, Ali AK, Komal AK, Lee SH (2014) The critical role of IL\u201015\u2010PI3K\u2010mTOR pathway in natural killer cell effector functions. Front Immunol 5: 187","journal-title":"Front Immunol"},{"key":"BFEMBR201948789_CR35","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/ni.2936","volume":"15","author":"A Marcais","year":"2014","unstructured":"Marcais A, Cherfils\u2010Vicini J, Viant C, Degouve S, Viel S, Fenis A, Rabilloud J, Mayol K, Tavares A, Bienvenu J et\u00a0al (2014) The metabolic checkpoint kinase mTOR is essential for IL\u201015 signaling during the development and activation of NK cells. Nat Immunol 15: 749\u2013757","journal-title":"Nat Immunol"},{"key":"BFEMBR201948789_CR36","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1084\/jem.183.5.2391","volume":"183","author":"H Arase","year":"1996","unstructured":"Arase H, Arase N, Saito T (1996) Interferon gamma production by natural killer (NK) cells and NK1.1+ T cells upon NKR\u2010P1 cross\u2010linking. J Exp Med 183: 2391\u20132396","journal-title":"J Exp Med"},{"key":"BFEMBR201948789_CR37","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/ni.2737","volume":"14","author":"E Vivier","year":"2013","unstructured":"Vivier E, Ugolini S, Nunes JA (2013) ADAPted secretion of cytokines in NK cells. Nat Immunol 14: 1108\u20131110","journal-title":"Nat Immunol"},{"key":"BFEMBR201948789_CR38","doi-asserted-by":"crossref","first-page":"999","DOI":"10.4049\/jimmunol.177.2.999","volume":"177","author":"VP Badovinac","year":"2006","unstructured":"Badovinac VP, Messingham KA, Griffith TS, Harty JT (2006) TRAIL deficiency delays, but does not prevent, erosion in the quality of \u201chelpless\u201d memory CD8 T cells. J Immunol 177: 999\u20131006","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR39","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1128\/JVI.78.5.2247-2254.2004","volume":"78","author":"G Bocharov","year":"2004","unstructured":"Bocharov G, Ludewig B, Bertoletti A, Klenerman P, Junt T, Krebs P, Luzyanina T, Fraser C, Anderson RM (2004) Underwhelming the immune response: effect of slow virus growth on CD8+\u2010T\u2010lymphocyte responses. J Virol 78: 2247\u20132254","journal-title":"J Virol"},{"key":"BFEMBR201948789_CR40","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1146\/annurev.immunol.16.1.359","volume":"16","author":"LL Lanier","year":"1998","unstructured":"Lanier LL (1998) NK cell receptors. Annu Rev Immunol 16: 359\u2013393","journal-title":"Annu Rev Immunol"},{"key":"BFEMBR201948789_CR41","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.immuni.2007.03.017","volume":"26","author":"L Lu","year":"2007","unstructured":"Lu L, Ikizawa K, Hu D, Werneck MB, Wucherpfennig KW, Cantor H (2007) Regulation of activated CD4+ T cells by NK cells via the Qa\u20101\u2010NKG2A inhibitory pathway. Immunity 26: 593\u2013604","journal-title":"Immunity"},{"key":"BFEMBR201948789_CR42","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1172\/JCI41264","volume":"120","author":"SN Waggoner","year":"2010","unstructured":"Waggoner SN, Taniguchi RT, Mathew PA, Kumar V, Welsh RM (2010) Absence of mouse 2B4 promotes NK cell\u2010mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis. J Clin Invest 120: 1925\u20131938","journal-title":"J Clin Invest"},{"key":"BFEMBR201948789_CR43","doi-asserted-by":"crossref","first-page":"4981","DOI":"10.4049\/jimmunol.177.8.4981","volume":"177","author":"AR French","year":"2006","unstructured":"French AR, Sjolin H, Kim S, Koka R, Yang L, Young DA, Cerboni C, Tomasello E, Ma A, Vivier E et\u00a0al (2006) DAP12 signaling directly augments proproliferative cytokine stimulation of NK cells during viral infections. J Immunol 177: 4981\u20134990","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR44","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1084\/jem.20090168","volume":"206","author":"MT Orr","year":"2009","unstructured":"Orr MT, Sun JC, Hesslein DG, Arase H, Phillips JH, Takai T, Lanier LL (2009) Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection. J Exp Med 206: 807\u2013817","journal-title":"J Exp Med"},{"key":"BFEMBR201948789_CR45","doi-asserted-by":"crossref","first-page":"7922","DOI":"10.1128\/JVI.00199-15","volume":"89","author":"BE Freeman","year":"2015","unstructured":"Freeman BE, Raue HP, Hill AB, Slifka MK (2015) Cytokine\u2010mediated activation of NK cells during viral infection. J Virol 89: 7922\u20137931","journal-title":"J Virol"},{"key":"BFEMBR201948789_CR46","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.immuni.2004.11.008","volume":"21","author":"GE Diehl","year":"2004","unstructured":"Diehl GE, Yue HH, Hsieh K, Kuang AA, Ho M, Morici LA, Lenz LL, Cado D, Riley LW, Winoto A (2004) TRAIL\u2010R as a negative regulator of innate immune cell responses. Immunity 21: 877\u2013889","journal-title":"Immunity"},{"key":"BFEMBR201948789_CR47","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.4049\/jimmunol.0901872","volume":"183","author":"JC Sun","year":"2009","unstructured":"Sun JC, Ma A, Lanier LL (2009) Cutting edge: IL\u201015\u2010independent NK cell response to mouse cytomegalovirus infection. J Immunol 183: 2911\u20132914","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR48","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3389\/fimmu.2013.00450","volume":"4","author":"A Marcais","year":"2013","unstructured":"Marcais A, Viel S, Grau M, Henry T, Marvel J, Walzer T (2013) Regulation of mouse NK cell development and function by cytokines. Front Immunol 4: 450","journal-title":"Front Immunol"},{"key":"BFEMBR201948789_CR49","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1182\/blood-2010-06-291633","volume":"117","author":"E Eckelhart","year":"2011","unstructured":"Eckelhart E, Warsch W, Zebedin E, Simma O, Stoiber D, Kolbe T, Rulicke T, Mueller M, Casanova E, Sexl V (2011) A novel Ncr1\u2010Cre mouse reveals the essential role of STAT5 for NK\u2010cell survival and development. Blood 117: 1565\u20131573","journal-title":"Blood"},{"key":"BFEMBR201948789_CR50","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1161\/01.CIR.0000062702.60708.C4","volume":"107","author":"P Secchiero","year":"2003","unstructured":"Secchiero P, Gonelli A, Carnevale E, Milani D, Pandolfi A, Zella D, Zauli G (2003) TRAIL promotes the survival and proliferation of primary human vascular endothelial cells by activating the Akt and ERK pathways. Circulation 107: 2250\u20132256","journal-title":"Circulation"},{"key":"BFEMBR201948789_CR51","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/jcp.20202","volume":"202","author":"G Zauli","year":"2005","unstructured":"Zauli G, Sancilio S, Cataldi A, Sabatini N, Bosco D, Di Pietro R (2005) PI\u20103K\/Akt and NF\u2010kappaB\/IkappaBalpha pathways are activated in Jurkat T cells in response to TRAIL treatment. J Cell Physiol 202: 900\u2013911","journal-title":"J Cell Physiol"},{"key":"BFEMBR201948789_CR52","doi-asserted-by":"crossref","first-page":"e10226","DOI":"10.1371\/journal.pone.0010226","volume":"5","author":"J Xu","year":"2010","unstructured":"Xu J, Zhou JY, Wei WZ, Wu GS (2010) Activation of the Akt survival pathway contributes to TRAIL resistance in cancer cells. PLoS ONE 5: e10226","journal-title":"PLoS ONE"},{"key":"BFEMBR201948789_CR53","first-page":"4651","volume":"125","author":"K Azijli","year":"2012","unstructured":"Azijli K, Yuvaraj S, Peppelenbosch MP, Wurdinger T, Dekker H, Joore J, van Dijk E, Quax WJ, Peters GJ, de Jong S et\u00a0al (2012) Kinome profiling of non\u2010canonical TRAIL signaling reveals RIP1\u2010Src\u2010STAT3\u2010dependent invasion in resistant non\u2010small cell lung cancer cells. J Cell Sci 125: 4651\u20134661","journal-title":"J Cell Sci"},{"key":"BFEMBR201948789_CR54","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1016\/j.biocel.2007.02.007","volume":"39","author":"C Falschlehner","year":"2007","unstructured":"Falschlehner C, Emmerich CH, Gerlach B, Walczak H (2007) TRAIL signalling: decisions between life and death. Int J Biochem Cell Biol 39: 1462\u20131475","journal-title":"Int J Biochem Cell Biol"},{"key":"BFEMBR201948789_CR55","doi-asserted-by":"crossref","first-page":"8407","DOI":"10.1128\/JVI.75.18.8407-8423.2001","volume":"75","author":"R Ou","year":"2001","unstructured":"Ou R, Zhou S, Huang L, Moskophidis D (2001) Critical role for alpha\/beta and gamma interferons in persistence of lymphocytic choriomeningitis virus by clonal exhaustion of cytotoxic T cells. J Virol 75: 8407\u20138423","journal-title":"J Virol"},{"key":"BFEMBR201948789_CR56","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1128\/jvi.68.3.1951-1955.1994","volume":"68","author":"D Moskophidis","year":"1994","unstructured":"Moskophidis D, Battegay M, Bruendler MA, Laine E, Gresser I, Zinkernagel RM (1994) Resistance of lymphocytic choriomeningitis virus to alpha\/beta interferon and to gamma interferon. J Virol 68: 1951\u20131955","journal-title":"J Virol"},{"key":"BFEMBR201948789_CR57","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1002\/eji.1830190720","volume":"19","author":"A Wille","year":"1989","unstructured":"Wille A, Gessner A, Lother H, Lehmann\u2010Grube F (1989) Mechanism of recovery from acute virus infection. VIII. Treatment of lymphocytic choriomeningitis virus\u2010infected mice with anti\u2010interferon\u2010gamma monoclonal antibody blocks generation of virus\u2010specific cytotoxic T lymphocytes and virus elimination. Eur J Immunol 19: 1283\u20131288","journal-title":"Eur J Immunol"},{"key":"BFEMBR201948789_CR58","doi-asserted-by":"crossref","first-page":"10304","DOI":"10.1128\/JVI.74.22.10304-10311.2000","volume":"74","author":"C Bartholdy","year":"2000","unstructured":"Bartholdy C, Christensen JP, Wodarz D, Thomsen AR (2000) Persistent virus infection despite chronic cytotoxic T\u2010lymphocyte activation in gamma interferon\u2010deficient mice infected with lymphocytic choriomeningitis virus. J Virol 74: 10304\u201310311","journal-title":"J Virol"},{"key":"BFEMBR201948789_CR59","doi-asserted-by":"crossref","first-page":"e2836","DOI":"10.1038\/cddis.2017.67","volume":"8","author":"P Bhat","year":"2017","unstructured":"Bhat P, Leggatt G, Waterhouse N, Frazer IH (2017) Interferon\u2010gamma derived from cytotoxic lymphocytes directly enhances their motility and cytotoxicity. Cell Death Dis 8: e2836","journal-title":"Cell Death Dis"},{"key":"BFEMBR201948789_CR60","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.4049\/jimmunol.177.5.3004","volume":"177","author":"JA Hollenbaugh","year":"2006","unstructured":"Hollenbaugh JA, Dutton RW (2006) IFN\u2010gamma regulates donor CD8 T cell expansion, migration, and leads to apoptosis of cells of a solid tumor. J Immunol 177: 3004\u20133011","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR61","first-page":"3399","volume":"61","author":"C Nakajima","year":"2001","unstructured":"Nakajima C, Uekusa Y, Iwasaki M, Yamaguchi N, Mukai T, Gao P, Tomura M, Ono S, Tsujimura T, Fujiwara H et\u00a0al (2001) A role of interferon\u2010gamma (IFN\u2010gamma) in tumor immunity: T cells with the capacity to reject tumor cells are generated but fail to migrate to tumor sites in IFN\u2010gamma\u2010deficient mice. Cancer Res 61: 3399\u20133405","journal-title":"Cancer Res"},{"key":"BFEMBR201948789_CR62","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1182\/blood-2007-11-123513","volume":"112","author":"O Gross","year":"2008","unstructured":"Gross O, Grupp C, Steinberg C, Zimmermann S, Strasser D, Hannesschlager N, Reindl W, Jonsson H, Huo H, Littman DR et\u00a0al (2008) Multiple ITAM\u2010coupled NK\u2010cell receptors engage the Bcl10\/Malt1 complex via Carma1 for NF\u2010kappaB and MAPK activation to selectively control cytokine production. Blood 112: 2421\u20132428","journal-title":"Blood"},{"key":"BFEMBR201948789_CR63","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/ni.2708","volume":"14","author":"K Rajasekaran","year":"2013","unstructured":"Rajasekaran K, Kumar P, Schuldt KM, Peterson EJ, Vanhaesebroeck B, Dixit V, Thakar MS, Malarkannan S (2013) Signaling by Fyn\u2010ADAP via the Carma1\u2010Bcl\u201010\u2010MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells. Nat Immunol 14: 1127\u20131136","journal-title":"Nat Immunol"},{"key":"BFEMBR201948789_CR64","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/nri3065","volume":"11","author":"FD Shi","year":"2011","unstructured":"Shi FD, Ljunggren HG, La Cava A, Van Kaer L (2011) Organ\u2010specific features of natural killer cells. Nat Rev Immunol 11: 658\u2013671","journal-title":"Nat Rev Immunol"},{"key":"BFEMBR201948789_CR65","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1067\/msy.2002.125311","volume":"132","author":"B Badgwell","year":"2002","unstructured":"Badgwell B, Parihar R, Magro C, Dierksheide J, Russo T, Carson WE III (2002) Natural killer cells contribute to the lethality of a murine model of Escherichia coli infection. Surgery 132: 205\u2013212","journal-title":"Surgery"},{"key":"BFEMBR201948789_CR66","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.micinf.2005.02.011","volume":"7","author":"AR Kerr","year":"2005","unstructured":"Kerr AR, Kirkham LA, Kadioglu A, Andrew PW, Garside P, Thompson H, Mitchell TJ (2005) Identification of a detrimental role for NK cells in pneumococcal pneumonia and sepsis in immunocompromised hosts. Microbes Infect 7: 845\u2013852","journal-title":"Microbes Infect"},{"key":"BFEMBR201948789_CR67","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.4049\/jimmunol.178.9.5779","volume":"178","author":"DS Hansen","year":"2007","unstructured":"Hansen DS, Bernard NJ, Nie CQ, Schofield L (2007) NK cells stimulate recruitment of CXCR3+ T cells to the brain during Plasmodium berghei\u2010mediated cerebral malaria. J Immunol 178: 5779\u20135788","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR68","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1128\/JVI.06209-11","volume":"86","author":"F Li","year":"2012","unstructured":"Li F, Zhu H, Sun R, Wei H, Tian Z (2012) Natural killer cells are involved in acute lung immune injury caused by respiratory syncytial virus infection. J Virol 86: 2251\u20132258","journal-title":"J Virol"},{"key":"BFEMBR201948789_CR69","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1002\/eji.200535342","volume":"36","author":"M Alsharifi","year":"2006","unstructured":"Alsharifi M, Lobigs M, Simon MM, Kersten A, Muller K, Koskinen A, Lee E, Mullbacher A (2006) NK cell\u2010mediated immunopathology during an acute viral infection of the CNS. Eur J Immunol 36: 887\u2013896","journal-title":"Eur J Immunol"},{"key":"BFEMBR201948789_CR70","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1002\/1521-4141(200208)32:8<2246::AID-IMMU2246>3.0.CO;2-6","volume":"32","author":"LM Sedger","year":"2002","unstructured":"Sedger LM, Glaccum MB, Schuh JC, Kanaly ST, Williamson E, Kayagaki N, Yun T, Smolak P, Le T, Goodwin R et\u00a0al (2002) Characterization of the in\u00a0vivo function of TNF\u2010alpha\u2010related apoptosis\u2010inducing ligand, TRAIL\/Apo2L, using TRAIL\/Apo2L gene\u2010deficient mice. Eur J Immunol 32: 2246\u20132254","journal-title":"Eur J Immunol"},{"key":"BFEMBR201948789_CR71","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/369031a0","volume":"369","author":"D Kagi","year":"1994","unstructured":"Kagi D, Ledermann B, Burki K, Seiler P, Odermatt B, Olsen KJ, Podack ER, Zinkernagel RM, Hengartner H (1994) Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin\u2010deficient mice. Nature 369: 31\u201337","journal-title":"Nature"},{"key":"BFEMBR201948789_CR72","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/346629a0","volume":"346","author":"H Pircher","year":"1990","unstructured":"Pircher H, Moskophidis D, Rohrer U, Burki K, Hengartner H, Zinkernagel RM (1990) Viral escape by selection of cytotoxic T cell\u2010resistant virus variants in\u00a0vivo. Nature 346: 629\u2013633","journal-title":"Nature"},{"key":"BFEMBR201948789_CR73","doi-asserted-by":"crossref","first-page":"4525","DOI":"10.4049\/jimmunol.176.8.4525","volume":"176","author":"P Aichele","year":"2006","unstructured":"Aichele P, Unsoeld H, Koschella M, Schweier O, Kalinke U, Vucikuja S (2006) CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion. J Immunol 176: 4525\u20134529","journal-title":"J Immunol"},{"key":"BFEMBR201948789_CR74","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/ni1207","volume":"6","author":"Z Jiang","year":"2005","unstructured":"Jiang Z, Georgel P, Du X, Shamel L, Sovath S, Mudd S, Huber M, Kalis C, Keck S, Galanos C et\u00a0al (2005) CD14 is required for MyD88\u2010independent LPS signaling. Nat Immunol 6: 565\u2013570","journal-title":"Nat Immunol"},{"key":"BFEMBR201948789_CR75","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1158\/0008-5472.CAN-17-0387","volume":"77","author":"JW Lau","year":"2017","unstructured":"Lau JW, Lehnert E, Sethi A, Malhotra R, Kaushik G, Onder Z, Groves\u2010Kirkby N, Mihajlovic A, DiGiovanna J, Srdic M et\u00a0al (2017) The cancer genomics cloud: collaborative, reproducible, and democratized\u2010A new paradigm in large\u2010scale computational research. Cancer Res 77: e3\u2013e6","journal-title":"Cancer Res"},{"key":"BFEMBR201948789_CR76","unstructured":"Andrews S (2010) FastQC: a quality control tool for high throughput sequence data. (http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc)"},{"key":"BFEMBR201948789_CR77","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR (2013) STAR: ultrafast universal RNA\u2010seq aligner. Bioinformatics 29: 15\u201321","journal-title":"Bioinformatics"},{"key":"BFEMBR201948789_CR78","doi-asserted-by":"crossref","first-page":"D754","DOI":"10.1093\/nar\/gkx1098","volume":"46","author":"DR Zerbino","year":"2018","unstructured":"Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, Billis K, Cummins C, Gall A, Giron CG et\u00a0al (2018) Ensembl 2018. Nucleic Acids Res 46: D754\u2013D761","journal-title":"Nucleic Acids Res"},{"key":"BFEMBR201948789_CR79","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders S, Pyl PT, Huber W (2015) HTSeq\u2013a Python framework to work with high\u2010throughput sequencing data. Bioinformatics 31: 166\u2013169","journal-title":"Bioinformatics"},{"key":"BFEMBR201948789_CR80","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA\u2010seq data with DESeq2. Genome Biol 15: 550","journal-title":"Genome Biol"},{"key":"BFEMBR201948789_CR81","first-page":"30","volume":"4","author":"T Koutsandreas","year":"2016","unstructured":"Koutsandreas T, Binenbaum I, Pilalis E, Valavanis I, Papadodima O, Chatziioannou A (2016) Analyzing and visualizing genomic complexity for the derivation of the emergent molecular networks. Int J Monit Surveill Technol Res 4: 30\u201349","journal-title":"Int J Monit Surveill Technol Res"},{"key":"BFEMBR201948789_CR82","doi-asserted-by":"crossref","first-page":"D472","DOI":"10.1093\/nar\/gkt1102","volume":"42","author":"D Croft","year":"2014","unstructured":"Croft D, Mundo AF, Haw R, Milacic M, Weiser J, Wu G, Caudy M, Garapati P, Gillespie M, Kamdar MR et\u00a0al (2014) The reactome pathway knowledgebase. Nucleic Acids Res 42: D472\u2013D477","journal-title":"Nucleic Acids Res"},{"key":"BFEMBR201948789_CR83","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ (2008) Analyzing real\u2010time PCR data by the comparative C(T) method. Nat Protoc 3: 1101\u20131108","journal-title":"Nat Protoc"}],"container-title":["The EMBO Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embr.201948789.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/embr.201948789","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/embr.201948789\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/embr.201948789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embr.201948789.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:36:24Z","timestamp":1779111384000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/embr.201948789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,19]]},"references-count":83,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1,7]]}},"alternative-id":["BFEMBR201948789"],"URL":"https:\/\/doi.org\/10.15252\/embr.201948789","relation":{},"ISSN":["1469-221X","1469-3178"],"issn-type":[{"value":"1469-221X","type":"print"},{"value":"1469-3178","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,19]]},"assertion":[{"value":"3 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMBR201948789"}}