{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:49:10Z","timestamp":1791355750282,"version":"4.3.1"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T00:00:00Z","timestamp":1477526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T00:00:00Z","timestamp":1477526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epidemiological evidence from the current outbreak of Zika virus (ZIKV) and recent studies in animal models indicate a strong causal link between ZIKV and microcephaly. ZIKV infection induces cell-cycle arrest and apoptosis in proliferating neural progenitors. However, the mechanisms leading to these phenotypes are still largely obscure. In this report, we explored the possible similarities between transcriptional responses induced by ZIKV in human neural progenitors and those elicited by three different genetic mutations leading to severe forms of microcephaly in mice. We found that the strongest similarity between all these conditions is the activation of common P53 downstream genes. In agreement with these observations, we report that ZIKV infection increases total P53 levels and nuclear accumulation, as well as P53 Ser15 phosphorylation, correlated with genotoxic stress and apoptosis induction. Interestingly, increased P53 activation and apoptosis are induced not only in cells expressing high levels of viral antigens but also in cells showing low or undetectable levels of the same proteins. These results indicate that P53 activation is an early and specific event in ZIKV-infected cells, which could result from cell-autonomous and\/or non-cell-autonomous mechanisms. Moreover, we highlight a small group of P53 effector proteins that could act as critical mediators, not only in ZIKV-induced microcephaly but also in many genetic microcephaly syndromes.<\/jats:p>","DOI":"10.1038\/cddis.2016.266","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T08:55:57Z","timestamp":1477558557000},"page":"e2440-e2440","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly and p53"],"prefix":"10.1038","volume":"7","author":[{"given":"Vincent El","family":"Ghouzzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico T","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Molineris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan C","family":"Mounce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia E","family":"Berto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Rak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lebon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Aubry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Tocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Gai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra MA","family":"Chiotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Sgr\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmarco","family":"Pallavicini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Simon-Loriere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Passemard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Vignuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Gressens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"Di Cunto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,27]]},"reference":[{"key":"BFcddis2016266_CR1","doi-asserted-by":"publisher","first-page":"547986","DOI":"10.1155\/2014\/547986","volume":"2014","author":"M Barbelanne","year":"2014","unstructured":"Barbelanne M, Tsang WY . Molecular and cellular basis of autosomal recessive primary microcephaly. Biomed Res Int 2014; 2014: 547986.","journal-title":"Biomed Res Int"},{"key":"BFcddis2016266_CR2","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.molmed.2006.06.006","volume":"12","author":"J Cox","year":"2006","unstructured":"Cox J, Jackson AP, Bond J, Woods CG . What primary microcephaly can tell us about brain growth. Trends Mol Med 2006; 12: 358\u2013366.","journal-title":"Trends Mol Med"},{"key":"BFcddis2016266_CR3","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1750-1172-6-39","volume":"6","author":"S Mahmood","year":"2011","unstructured":"Mahmood S, Ahmad W, Hassan MJ . Autosomal recessive primary microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum. Orphanet J Rare Dis 2011; 6: 39.","journal-title":"Orphanet J Rare Dis"},{"key":"BFcddis2016266_CR4","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/B978-0-444-52891-9.00013-0","volume":"111","author":"S Passemard","year":"2013","unstructured":"Passemard S, Kaindl AM, Verloes A . Microcephaly. Handb Clin Neurol 2013; 111: 129\u2013141.","journal-title":"Handb Clin Neurol"},{"key":"BFcddis2016266_CR5","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1136\/archdischild-2012-302882","volume":"98","author":"CG Woods","year":"2013","unstructured":"Woods CG, Parker A . Investigating microcephaly. Arch Dis Child 2013; 98: 707\u2013713.","journal-title":"Arch Dis Child"},{"key":"BFcddis2016266_CR6","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.spen.2007.07.003","volume":"14","author":"D Abuelo","year":"2007","unstructured":"Abuelo D . Microcephaly syndromes. Semin Pediatr Neurol 2007; 14: 118\u2013127.","journal-title":"Semin Pediatr Neurol"},{"key":"BFcddis2016266_CR7","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.mcp.2015.05.015","volume":"29","author":"DJ Morris-Rosendahl","year":"2015","unstructured":"Morris-Rosendahl DJ, Kaindl AM . What next-generation sequencing (NGS) technology has enabled us to learn about primary autosomal recessive microcephaly (MCPH). Mol Cell Probes 2015; 29: 271\u2013281.","journal-title":"Mol Cell Probes"},{"key":"BFcddis2016266_CR8","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1056\/NEJMoa1601824","volume":"374","author":"RW Driggers","year":"2016","unstructured":"Driggers RW, Ho CY, Korhonen EM, Kuivanen S, Jaaskelainen AJ, Smura T et al. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med 2016; 374: 2142\u20132151.","journal-title":"N Engl J Med"},{"key":"BFcddis2016266_CR9","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1056\/NEJMoa1600651","volume":"374","author":"J Mlakar","year":"2016","unstructured":"Mlakar J, Korva M, Tul N, Popovic M, Poljsak-Prijatelj M, Mraz J et al. Zika virus associated with microcephaly. N Engl J Med 2016; 374: 951\u2013958.","journal-title":"N Engl J Med"},{"key":"BFcddis2016266_CR10","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1056\/NEJMra1602113","volume":"374","author":"LR Petersen","year":"2016","unstructured":"Petersen LR, Jamieson DJ, Powers AM, Honein MA . Zika Virus. N Engl J Med 2016; 374: 1552\u20131563.","journal-title":"N Engl J Med"},{"key":"BFcddis2016266_CR11","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/S1473-3099(16)00095-5","volume":"16","author":"G Calvet","year":"2016","unstructured":"Calvet G, Aguiar RS, Melo AS, Sampaio SA, de Filippis I, Fabri A et al. Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis 2016; 16: 653\u2013660.","journal-title":"Lancet Infect Dis"},{"key":"BFcddis2016266_CR12","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.stem.2016.02.016","volume":"18","author":"H Tang","year":"2016","unstructured":"Tang H, Hammack C, Ogden SC, Wen Z, Qian X, Li Y et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell 2016; 18: 587\u2013590.","journal-title":"Cell Stem Cell"},{"key":"BFcddis2016266_CR13","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.stem.2016.04.014","volume":"19","author":"J Dang","year":"2016","unstructured":"Dang J, Tiwari SK, Lichinchi G, Qin Y, Patil VS, Eroshkin AM et al. Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell 2016; 19: 258\u2013265.","journal-title":"Cell Stem Cell"},{"key":"BFcddis2016266_CR14","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.aaf6116","volume":"352","author":"PP Garcez","year":"2016","unstructured":"Garcez PP, Loiola EC, Madeiro da Costa R, Higa LM, Trindade P, Delvecchio R et al. Zika virus impairs growth in human neurospheres and brain organoids. Science 2016; 352: 816\u2013818.","journal-title":"Science"},{"key":"BFcddis2016266_CR15","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1016\/j.cell.2016.04.032","volume":"165","author":"X Qian","year":"2016","unstructured":"Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 2016; 165: 1238\u20131254.","journal-title":"Cell"},{"key":"BFcddis2016266_CR16","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.stem.2016.04.017","volume":"19","author":"C Li","year":"2016","unstructured":"Li C, Xu D, Ye Q, Hong S, Jiang Y, Liu X et al. Zika virus disrupts neural progenitor development and leads to microcephaly in mice. Cell Stem Cell 2016; 19: 120\u2013126.","journal-title":"Cell Stem Cell"},{"key":"BFcddis2016266_CR17","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/nature18296","volume":"534","author":"F Cugola","year":"2016","unstructured":"Cugola F, Fernandes I, Russo F, Freitas B, Dias J, Guimar\u00e3es K et al. The Brazilian Zika virus strain causes birth defects in experimental models. Nature 2016; 534: 267\u2013271.","journal-title":"Nature"},{"key":"BFcddis2016266_CR18","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/j.cell.2016.05.008","volume":"165","author":"JJ Miner","year":"2016","unstructured":"Miner JJ, Cao B, Govero J, Smith AM, Fernandez E, Cabrera OH et al. Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell 2016; 165: 1081\u20131091.","journal-title":"Cell"},{"key":"BFcddis2016266_CR19","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/cr.2016.58","volume":"26","author":"KY Wu","year":"2016","unstructured":"Wu KY, Zuo GL, Li XF, Ye Q, Deng YQ, Huang XY et al. Vertical transmission of Zika virus targeting the radial glial cells affects cortex development of offspring mice. Cell Res 2016; 26: 645\u2013654.","journal-title":"Cell Res"},{"key":"BFcddis2016266_CR20","doi-asserted-by":"publisher","first-page":"8880","DOI":"10.1128\/JVI.00354-15","volume":"89","author":"R Hamel","year":"2015","unstructured":"Hamel R, Dejarnac O, Wichit S, Ekchariyawat P, Neyret A, Luplertlop N et al. Biology of zika virus infection in human skin cells. J Virol 2015; 89: 8880\u20138896.","journal-title":"J Virol"},{"key":"BFcddis2016266_CR21","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1099\/0022-1317-30-1-123","volume":"30","author":"JH Way","year":"1976","unstructured":"Way JH, Bowen ET, Platt GS . Comparative studies of some African arboviruses in cell culture and in mice. J Gen Virol 1976; 30: 123\u2013130.","journal-title":"J Gen Virol"},{"key":"BFcddis2016266_CR22","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.stem.2016.03.012","volume":"18","author":"TJ Nowakowski","year":"2016","unstructured":"Nowakowski TJ, Pollen AA, Di Lullo E, Sandoval-Espinosa C, Bershteyn M, Kriegstein AR . Expression analysis highlights AXL as a candidate zika virus entry receptor in neural stem cells. Cell Stem Cell 2016; 18: 591\u2013596.","journal-title":"Cell Stem Cell"},{"key":"BFcddis2016266_CR23","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/ajmg.c.31397","volume":"166C","author":"D Alcantara","year":"2014","unstructured":"Alcantara D, O'Driscoll M . Congenital microcephaly. Am J Med Genet C 2014; 166C: 124\u2013139.","journal-title":"Am J Med Genet C"},{"key":"BFcddis2016266_CR24","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0896-6273(00)00090-8","volume":"28","author":"F Di Cunto","year":"2000","unstructured":"Di Cunto F, Imarisio S, Hirsch E, Broccoli V, Bulfone A, Migheli A et al. Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis. Neuron 2000; 28: 115\u2013127.","journal-title":"Neuron"},{"key":"BFcddis2016266_CR25","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nn.2527","volume":"13","author":"DL Silver","year":"2010","unstructured":"Silver DL, Watkins-Chow DE, Schreck KC, Pierfelice TJ, Larson DM, Burnetti AJ et al. The exon junction complex component Magoh controls brain size by regulating neural stem cell division. Nat Neurosci 2010; 13: 551\u2013558.","journal-title":"Nat Neurosci"},{"key":"BFcddis2016266_CR26","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.devcel.2015.11.005","volume":"35","author":"S Laguesse","year":"2015","unstructured":"Laguesse S, Creppe C, Nedialkova DD, Prevot PP, Borgs L, Huysseune S et al. A Dynamic unfolded protein response contributes to the control of cortical neurogenesis. Dev Cell 2015; 35: 553\u2013567.","journal-title":"Dev Cell"},{"key":"BFcddis2016266_CR27","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/cdd.2015.142","volume":"23","author":"F Sgro","year":"2015","unstructured":"Sgro F, Bianchi FT, Falcone M, Pallavicini G, Gai M, Chiotto AM et al. Tissue-specific control of midbody microtubule stability by Citron kinase through modulation of TUBB3 phosphorylation. Cell Death Differ 2015; 23: 801\u2013813.","journal-title":"Cell Death Differ"},{"key":"BFcddis2016266_CR28","doi-asserted-by":"publisher","first-page":"3768","DOI":"10.1091\/mbc.e10-12-0952","volume":"22","author":"M Gai","year":"2011","unstructured":"Gai M, Camera P, Dema A, Bianchi F, Berto G, Scarpa E et al. Citron kinase controls abscission through RhoA and anillin. Mol Biol Cell 2011; 22: 3768\u20133778.","journal-title":"Mol Biol Cell"},{"key":"BFcddis2016266_CR29","doi-asserted-by":"publisher","first-page":"9782","DOI":"10.1073\/pnas.1301328110","volume":"110","author":"ZI Bassi","year":"2013","unstructured":"Bassi ZI, Audusseau M, Riparbelli MG, Callaini G, D'Avino PP . Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proc Natl Acad Sci USA 2013; 110: 9782\u20139787.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2016266_CR30","doi-asserted-by":"publisher","first-page":"RC217","DOI":"10.1523\/JNEUROSCI.22-08-j0001.2002","volume":"22","author":"MR Sarkisian","year":"2002","unstructured":"Sarkisian MR, Li W, Di Cunto F, D'Mello SR, LoTurco JJ . Citron-kinase, a protein essential to cytokinesis in neuronal progenitors, is deleted in the flathead mutant rat. J Neurosci 2002;22: RC217.","journal-title":"J Neurosci"},{"key":"BFcddis2016266_CR31","doi-asserted-by":"crossref","unstructured":"McMahon JJ, Miller EE, Silver DL . The exon junction complex in neural development and neurodevelopmental disease. Int J Dev Neurosci 2016.","DOI":"10.1016\/j.ijdevneu.2016.03.006"},{"key":"BFcddis2016266_CR32","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.neuron.2015.12.007","volume":"89","author":"LJ Pilaz","year":"2016","unstructured":"Pilaz LJ, McMahon JJ, Miller EE, Lennox AL, Suzuki A, Salmon E et al. Prolonged mitosis of neural progenitors alters cell fate in the developing brain. Neuron 2016; 89: 83\u201399.","journal-title":"Neuron"},{"key":"BFcddis2016266_CR33","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/S1097-2765(00)80194-X","volume":"4","author":"BO Wittschieben","year":"1999","unstructured":"Wittschieben BO, Otero G, de Bizemont T, Fellows J, Erdjument-Bromage H, Ohba R et al. A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme. Mol Cell 1999; 4: 123\u2013128.","journal-title":"Mol Cell"},{"key":"BFcddis2016266_CR34","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.4161\/15476286.2014.992276","volume":"11","author":"T Karlsborn","year":"2014","unstructured":"Karlsborn T, Tukenmez H, Mahmud AK, Xu F, Xu H, Bystrom AS . Elongator, a conserved complex required for wobble uridine modifications in eukaryotes. RNA Biol 2014; 11: 1519\u20131528.","journal-title":"RNA Biol"},{"key":"BFcddis2016266_CR35","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1073\/pnas.0308600100","volume":"101","author":"W Haubensak","year":"2004","unstructured":"Haubensak W, Attardo A, Denk W, Huttner WB . Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci USA 2004; 101: 3196\u20133201.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2016266_CR36","doi-asserted-by":"publisher","first-page":"6275","DOI":"10.1523\/JNEUROSCI.0532-12.2012","volume":"32","author":"RD Hodge","year":"2012","unstructured":"Hodge RD, Nelson BR, Kahoud RJ, Yang R, Mussar KE, Reiner SL et al. Tbr2 is essential for hippocampal lineage progression from neural stem cells to intermediate progenitors and neurons. J Neurosci 2012; 32: 6275\u20136287.","journal-title":"J Neurosci"},{"key":"BFcddis2016266_CR37","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"W da Huang","year":"2009","unstructured":"da Huang W, Sherman BT, Lempicki RA . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4: 44\u201357.","journal-title":"Nat Protoc"},{"key":"BFcddis2016266_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","volume":"37","author":"Huang","year":"2009","unstructured":"Huang, da W, Sherman BT, Lempicki RA . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37: 1\u201313.","journal-title":"Nucleic Acids Res"},{"key":"BFcddis2016266_CR39","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/ng1180","volume":"34","author":"VK Mootha","year":"2003","unstructured":"Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003; 34: 267\u2013273.","journal-title":"Nat Genet"},{"key":"BFcddis2016266_CR40","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102: 15545\u201315550.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2016266_CR41","doi-asserted-by":"publisher","first-page":"3528","DOI":"10.1128\/JVI.02161-09","volume":"84","author":"MH Luo","year":"2010","unstructured":"Luo MH, Hannemann H, Kulkarni AS, Schwartz PH, O'Dowd JM, Fortunato EA . Human cytomegalovirus infection causes premature and abnormal differentiation of human neural progenitor cells. J Virol 2010; 84: 3528\u20133541.","journal-title":"J Virol"},{"key":"BFcddis2016266_CR42","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1016\/S0140-6736(16)00651-6","volume":"387","author":"S Cauchemez","year":"2016","unstructured":"Cauchemez S, Besnard M, Bompard P, Dub T, Guillemette-Artur P, Eyrolle-Guignot D et al. Association between Zika virus and microcephaly in French Polynesia, 2013\u201315: a retrospective study. Lancet 2016; 387: 2125\u20132132.","journal-title":"Lancet"},{"key":"BFcddis2016266_CR43","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1016\/S0140-6736(16)00742-X","volume":"387","author":"LC Rodrigues","year":"2016","unstructured":"Rodrigues LC . Microcephaly and Zika virus infection. Lancet 2016; 387: 2070\u20132072.","journal-title":"Lancet"},{"key":"BFcddis2016266_CR44","first-page":"2055","volume":"6","author":"G Shaulsky","year":"1991","unstructured":"Shaulsky G, Goldfinger N, Tosky MS, Levine AJ, Rotter V . Nuclear localization is essential for the activity of p53 protein. Oncogene 1991; 6: 2055\u20132065.","journal-title":"Oncogene"},{"key":"BFcddis2016266_CR45","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1128\/MCB.11.1.582","volume":"11","author":"D Ginsberg","year":"1991","unstructured":"Ginsberg D, Michael-Michalovitz D, Oren M . Induction of growth arrest by a temperature-sensitive p53 mutant is correlated with increased nuclear localization and decreased stability of the protein. Mol Cell Biol 1991; 11: 582\u2013585.","journal-title":"Mol Cell Biol"},{"key":"BFcddis2016266_CR46","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S0092-8674(00)80416-X","volume":"91","author":"SY Shieh","year":"1997","unstructured":"Shieh SY, Ikeda M, Taya Y, Prives C . DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 1997; 91: 325\u2013334.","journal-title":"Cell"},{"key":"BFcddis2016266_CR47","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3390\/biom6010002","volume":"6","author":"EL Ryan","year":"2016","unstructured":"Ryan EL, Hollingworth R, Grand RJ . Activation of the DNA damage response by RNA viruses. Biomolecules 2016; 6: 2.","journal-title":"Biomolecules"},{"key":"BFcddis2016266_CR48","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1146\/annurev-virology-031413-085548","volume":"1","author":"MA Luftig","year":"2014","unstructured":"Luftig MA . Viruses and the DNA damage response: activation and antagonism. Annu Rev Virol 2014; 1: 605\u2013625.","journal-title":"Annu Rev Virol"},{"key":"BFcddis2016266_CR49","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1093\/nar\/gkv061","volume":"43","author":"V Turinetto","year":"2015","unstructured":"Turinetto V, Giachino C . Multiple facets of histone variant H2AX: a DNA double-strand-break marker with several biological functions. Nucleic Acids Res 2015; 43: 2489\u20132498.","journal-title":"Nucleic Acids Res"},{"key":"BFcddis2016266_CR50","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.cell.2015.12.039","volume":"164","author":"PC Wei","year":"2016","unstructured":"Wei PC, Chang AN, Kao J, Du Z, Meyers RM, Alt FW et al. Long neural genes harbor recurrent DNA break clusters in neural stem\/progenitor cells. Cell 2016; 164: 644\u2013655.","journal-title":"Cell"},{"key":"BFcddis2016266_CR51","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1242\/dev.131516","volume":"143","author":"M Breuss","year":"2015","unstructured":"Breuss M, Fritz T, Gstrein T, Chan K, Ushakova L, Yu N et al. Mutations in the murine homologue of TUBB5 cause microcephaly by perturbing cell cycle progression and inducing p53-associated apoptosis. Development 2015; 143: 1126\u20131133.","journal-title":"Development"},{"key":"BFcddis2016266_CR52","doi-asserted-by":"publisher","first-page":"7676","DOI":"10.1038\/ncomms8676","volume":"6","author":"M Marjanovic","year":"2015","unstructured":"Marjanovic M, Sanchez-Huertas C, Terre B, Gomez R, Scheel JF, Pacheco S et al. CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination. Nat Commun 2015; 6: 7676.","journal-title":"Nat Commun"},{"key":"BFcddis2016266_CR53","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/j.celrep.2014.04.003","volume":"7","author":"A Pollock","year":"2014","unstructured":"Pollock A, Bian S, Zhang C, Chen Z, Sun T . Growth of the developing cerebral cortex is controlled by microRNA-7 through the p53 pathway. Cell Rep 2014; 7: 1184\u20131196.","journal-title":"Cell Rep"},{"key":"BFcddis2016266_CR54","doi-asserted-by":"publisher","first-page":"12570","DOI":"10.1523\/JNEUROSCI.4048-08.2008","volume":"28","author":"C Seah","year":"2008","unstructured":"Seah C, Levy MA, Jiang Y, Mokhtarzada S, Higgs DR, Gibbons RJ et al. Neuronal death resulting from targeted disruption of the Snf2 protein ATRX is mediated by p53. J Neurosci 2008; 28: 12570\u201312580.","journal-title":"J Neurosci"},{"key":"BFcddis2016266_CR55","doi-asserted-by":"publisher","first-page":"3921","DOI":"10.1242\/dev.124271","volume":"142","author":"SE Williams","year":"2015","unstructured":"Williams SE, Garcia I, Crowther AJ, Li S, Stewart A, Liu H et al. Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice. Development 2015; 142: 3921\u20133932.","journal-title":"Development"},{"key":"BFcddis2016266_CR56","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.ajhg.2015.01.017","volume":"96","author":"VA Arboleda","year":"2015","unstructured":"Arboleda VA, Lee H, Dorrani N, Zadeh N, Willis M, Macmurdo CF et al. De novo nonsense mutations in KAT6A, a lysine acetyl-transferase gene, cause a syndrome including microcephaly and global developmental delay. Am J Hum Genet 2015; 96: 498\u2013506.","journal-title":"Am J Hum Genet"},{"key":"BFcddis2016266_CR57","doi-asserted-by":"publisher","first-page":"4322","DOI":"10.1523\/JNEUROSCI.4815-07.2008","volume":"28","author":"TH Davis","year":"2008","unstructured":"Davis TH, Cuellar TL, Koch SM, Barker AJ, Harfe BD, McManus MT et al. Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus. J Neurosci 2008; 28: 4322\u20134330.","journal-title":"J Neurosci"},{"key":"BFcddis2016266_CR58","doi-asserted-by":"publisher","first-page":"3373","DOI":"10.1080\/15384101.2015.1090066","volume":"14","author":"I Lopez","year":"2015","unstructured":"Lopez I, Tournillon AS, Nylander K, Fahraeus R . p53-mediated control of gene expression via mRNA translation during endoplasmic reticulum stress. Cell Cycle 2015; 14: 3373\u20133378.","journal-title":"Cell Cycle"},{"key":"BFcddis2016266_CR59","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1101\/gad.1165804","volume":"18","author":"L Qu","year":"2004","unstructured":"Qu L, Huang S, Baltzis D, Rivas-Estilla AM, Pluquet O, Hatzoglou M et al. Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta. Genes Dev 2004; 18: 261\u2013277.","journal-title":"Genes Dev"},{"key":"BFcddis2016266_CR60","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/j.micinf.2008.06.005","volume":"10","author":"AM Nasirudeen","year":"2008","unstructured":"Nasirudeen AM, Wang L, Liu DX . Induction of p53-dependent and mitochondria-mediated cell death pathway by dengue virus infection of human and animal cells. Microbes Infect 2008; 10: 1124\u20131132.","journal-title":"Microbes Infect"},{"key":"BFcddis2016266_CR61","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1111\/j.1462-5822.2007.01081.x","volume":"10","author":"MR Yang","year":"2008","unstructured":"Yang MR, Lee SR, Oh W, Lee EW, Yeh JY, Nah JJ et al. West Nile virus capsid protein induces p53-mediated apoptosis via the sequestration of HDM2 to the nucleolus. Cell Microbiol 2008; 10: 165\u2013176.","journal-title":"Cell Microbiol"},{"key":"BFcddis2016266_CR62","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.virol.2009.06.039","volume":"391","author":"S Li","year":"2009","unstructured":"Li S, Ye L, Yu X, Xu B, Li K, Zhu X et al. Hepatitis C virus NS4B induces unfolded protein response and endoplasmic reticulum overload response-dependent NF-kappaB activation. Virology 2009; 391: 257\u2013264.","journal-title":"Virology"},{"key":"BFcddis2016266_CR63","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.virol.2016.03.006","volume":"493","author":"E Frumence","year":"2016","unstructured":"Frumence E, Roche M, Krejbich-Trotot P, El-Kalamouni C, Nativel B, Rondeau P et al. The South Pacific epidemic strain of Zika virus replicates efficiently in human epithelial A549 cells leading to IFN-beta production and apoptosis induction. Virology 2016; 493: 217\u2013226.","journal-title":"Virology"},{"key":"BFcddis2016266_CR64","doi-asserted-by":"publisher","first-page":"298","DOI":"10.3390\/v2010298","volume":"2","author":"C Rivas","year":"2010","unstructured":"Rivas C, Aaronson SA, Munoz-Fontela C . Dual role of p53 in innate antiviral immunity. Viruses 2010; 2: 298\u2013313.","journal-title":"Viruses"},{"key":"BFcddis2016266_CR65","doi-asserted-by":"publisher","first-page":"7852","DOI":"10.1073\/pnas.0812148106","volume":"106","author":"CH Yoon","year":"2009","unstructured":"Yoon CH, Lee ES, Lim DS, Bae YS . PKR, a p53 target gene, plays a crucial role in the tumor-suppressor function of p53. Proc Natl Acad Sci USA 2009; 106: 7852\u20137857.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2016266_CR66","doi-asserted-by":"publisher","first-page":"6557","DOI":"10.1128\/MCB.01202-08","volume":"28","author":"M Taura","year":"2008","unstructured":"Taura M, Eguma A, Suico MA, Shuto T, Koga T, Komatsu K et al. P53 regulates Toll-like receptor 3 expression and function in human epithelial cell lines. Mol Cell Biol 2008; 28: 6557\u20136567.","journal-title":"Mol Cell Biol"},{"key":"BFcddis2016266_CR67","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.bbrc.2009.07.073","volume":"388","author":"M Hirsch","year":"2009","unstructured":"Hirsch M, Knight J, Tobita M, Soltys J, Panitch H, Mao-Draayer Y . The effect of interferon-beta on mouse neural progenitor cell survival and differentiation. Biochem Biophys Res Commun 2009; 388: 181\u2013186.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFcddis2016266_CR68","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/j.chom.2016.05.009","volume":"19","author":"A Grant","year":"2016","unstructured":"Grant A, Ponia SS, Tripathi S, Balasubramaniam V, Miorin L, Sourisseau M et al. Zika virus targets human STAT2 to inhibit type I interferon signaling. Cell Host Microbe 2016; 19: 882\u2013890.","journal-title":"Cell Host Microbe"},{"key":"BFcddis2016266_CR69","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13578-016-0110-x","volume":"6","author":"AJ Rolfe","year":"2016","unstructured":"Rolfe AJ, Bosco DB, Wang J, Nowakowski RS, Fan J, Ren Y . Bioinformatic analysis reveals the expression of unique transcriptomic signatures in Zika virus infected human neural stem cells. Cell Biosci 2016; 6: 42.","journal-title":"Cell Biosci"},{"key":"BFcddis2016266_CR70","doi-asserted-by":"publisher","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","volume":"14","author":"D Kim","year":"2013","unstructured":"Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL . TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 2013; 14: R36.","journal-title":"Genome Biol"},{"key":"BFcddis2016266_CR71","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1126\/science.1172482","volume":"324","author":"J Yu","year":"2009","unstructured":"Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II et al. Human induced pluripotent stem cells free of vector and transgene sequences. Science 2009; 324: 797\u2013801.","journal-title":"Science"},{"key":"BFcddis2016266_CR72","doi-asserted-by":"publisher","first-page":"e294","DOI":"10.1038\/tp.2013.71","volume":"3","author":"C Boissart","year":"2013","unstructured":"Boissart C, Poulet A, Georges P, Darville H, Julita E, Delorme R et al. Differentiation from human pluripotent stem cells of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening. Transl Psychiatry 2013; 3: e294.","journal-title":"Transl Psychiatry"},{"key":"BFcddis2016266_CR73","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nbt.1529","volume":"27","author":"SM Chambers","year":"2009","unstructured":"Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L . Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 2009; 27: 275\u2013280.","journal-title":"Nat Biotechnol"},{"key":"BFcddis2016266_CR74","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T et al. Fiji: an open-source platform for biological-image analysis. Nat Methods 2012; 9: 676\u2013682.","journal-title":"Nat Methods"}],"updated-by":[{"DOI":"10.1038\/cddis.2016.446","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T00:00:00Z","timestamp":1484784000000}},{"DOI":"10.1038\/s41419-018-1159-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T00:00:00Z","timestamp":1542672000000}}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddis2016266.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016266","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016266.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T04:09:34Z","timestamp":1672805374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis2016266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,27]]},"references-count":74,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2016,10]]}},"alternative-id":["BFcddis2016266"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2016.266","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,27]]},"assertion":[{"value":"2 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}