{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T17:31:38Z","timestamp":1776533498141,"version":"3.51.2"},"reference-count":119,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T00:00:00Z","timestamp":1582675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The rubella virus (RV) was the first virus shown to be teratogenic in humans. The wealth of data on the clinical symptoms associated with congenital rubella syndrome is in stark contrast to an incomplete understanding of the forces leading to the teratogenic alterations in humans. This applies not only to RV, but also to congenital viral infections in general and includes (1) the mode of vertical transmission, even at early gestation, (2) the possible involvement of inflammation as a consequence of an activated innate immune response, and (3) the underlying molecular and cellular alterations. With the progress made in the development of pluripotent stem cell-based models including organoids and embryoids, it is now possible to assess congenital virus infections on a mechanistic level. Moreover, antiviral treatment options can be validated, and newly emerging viruses with a potential impact on human embryonal development, such as that recently reflected by the Zika virus (ZIKV), can be characterized. Here, we discuss human cytomegalovirus (HCMV) and ZIKV in comparison to RV as viruses with well-known congenital pathologies and highlight their analysis on current models for the early phase of human development. This includes the implications of their genetic variability and, as such, virus strain-specific properties for their use as archetype models for congenital virus infections. In this review, we will discuss the use of induced pluripotent stem cells (iPSC) and derived organoid systems for the study of congenital virus infections with a focus on their prominent aetiologies, HCMV, ZIKV, and RV. Their assessment on these models will provide valuable information on how human development is impaired by virus infections; it will also add new insights into the normal progression of human development through the analysis of developmental pathways in the context of virus-induced alterations. These are exciting perspectives for both developmental biology and congenital virology.<\/jats:p>","DOI":"10.3390\/cells9030542","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T03:21:16Z","timestamp":1582773676000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4962-6568","authenticated-orcid":false,"given":"Claudia","family":"Claus","sequence":"first","affiliation":[{"name":"Institute of Virology, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6808-6494","authenticated-orcid":false,"given":"Matthias","family":"Jung","sequence":"additional","affiliation":[{"name":"University Clinic and Outpatient Clinic for Psychiatry, Psychotherapy, Psychosomatic Medicine, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith M.","family":"H\u00fcbschen","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, 4354 Esch-sur-Alzette, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,26]]},"reference":[{"key":"ref_1","first-page":"170","article-title":"Congenital cataract following german measles in the mother. 1941","volume":"107","author":"Gregg","year":"1991","journal-title":"Problems Birth Defects"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/bdra.23029","article-title":"The all-or-none phenomenon revisited","volume":"94","author":"Adam","year":"2012","journal-title":"Birth Defects Res. Part. A Clin. Mol. Teratol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/aji.12289","article-title":"Understanding the complexity of the immune system during pregnancy","volume":"72","author":"Racicot","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1016\/j.celrep.2017.10.059","article-title":"Outcomes of congenital zika disease depend on timing of infection and maternal-fetal interferon action","volume":"21","author":"Chen","year":"2017","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.cell.2017.11.018","article-title":"Intrinsic immunity shapes viral resistance of stem cells","volume":"172","author":"Wu","year":"2018","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1073\/pnas.1812449116","article-title":"Type i interferon response impairs differentiation potential of pluripotent stem cells","volume":"116","author":"Eggenberger","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dukhovny, A., Lamkiewicz, K., Chen, Q., Fricke, M., Jabrane-Ferrat, N., Marz, M., Jung, J.U., and Sklan, E.H. (2019). A crispr activation screen identifies genes that protect against zika virus infection. J. Virol.","DOI":"10.3390\/proceedings2020050149"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chom.2016.03.008","article-title":"Type iii interferons produced by human placental trophoblasts confer protection against zika virus infection","volume":"19","author":"Bayer","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9433","DOI":"10.1073\/pnas.1707513114","article-title":"Organotypic models of type iii interferon-mediated protection from zika virus infections at the maternal-fetal interface","volume":"114","author":"Corry","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1016\/S0140-6736(88)92249-0","article-title":"Outcome of confirmed periconceptional maternal rubella","volume":"1","author":"Enders","year":"1988","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1002\/pd.4467","article-title":"Rubella and pregnancy: Diagnosis, management and outcomes","volume":"34","author":"Bouthry","year":"2014","journal-title":"Prenat. Diagn."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev-virology-031413-085524","article-title":"The placenta as a barrier to viral infections","volume":"1","author":"Sadovsky","year":"2014","journal-title":"Annu. Rev. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.chom.2017.04.007","article-title":"Microbial vertical transmission during human pregnancy","volume":"21","author":"Arora","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1146\/annurev-virology-092917-043236","article-title":"Congenital viral infection: Traversing the uterine-placental interface","volume":"5","author":"Pereira","year":"2018","journal-title":"Annu. Rev. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13204","DOI":"10.1128\/JVI.05749-11","article-title":"Modeling of human cytomegalovirus maternal-fetal transmission in a novel decidual organ culture","volume":"85","author":"Weisblum","year":"2011","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.2353\/ajpath.2006.050482","article-title":"Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal fc receptor-mediated transcytosis","volume":"168","author":"Maidji","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1038\/s41467-019-12063-2","article-title":"Pre- and peri-implantation zika virus infection impairs fetal development by targeting trophectoderm cells","volume":"10","author":"Tan","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.mam.2012.12.011","article-title":"Physiological and molecular determinants of embryo implantation","volume":"34","author":"Zhang","year":"2013","journal-title":"Mol. Aspects Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Massimiani, M., Lacconi, V., La Civita, F., Ticconi, C., Rago, R., and Campagnolo, L. (2019). Molecular signaling regulating endometrium-blastocyst crosstalk. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010023"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1099\/0022-1317-50-2-317","article-title":"Replication and expression of rubella virus in human lymphocyte populations","volume":"50","author":"Chantler","year":"1980","journal-title":"J. Gen. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zobel, S., Lorenz, M., Frascaroli, G., Bohnke, J., Bilz, N.C., Stanifer, M.L., Boulant, S., Bergs, S., Liebert, U.G., and Claus, C. (2018). Rubella virus strain-associated differences in the induction of oxidative stress are independent of their interferon activation. Viruses, 10.","DOI":"10.3390\/v10100540"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Trinh, Q.D., Pham, N.T.K., Takada, K., Komine-Aizawa, S., and Hayakawa, S. (2018). Myelin oligodendrocyte glycoprotein-independent rubella infection of keratinocytes and resistance of first-trimester trophoblast cells to rubella virus in vitro. Viruses, 10.","DOI":"10.3390\/v10010023"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1089\/088282404322875485","article-title":"Rubella virus does not induce apoptosis in primary human embryo fibroblast cultures: A possible way of viral persistence in congenital infection","volume":"17","author":"Adamo","year":"2004","journal-title":"Viral Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/S0022-3476(66)80204-4","article-title":"Fetal rubella pathology","volume":"68","author":"Tondury","year":"1966","journal-title":"J. Pediatrics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ebiom.2015.11.050","article-title":"Immunolocalization and distribution of rubella antigen in fatal congenital rubella syndrome","volume":"3","author":"Lazar","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/ar.1091330202","article-title":"Studies on the mechanism of teratogenic action of trypan blue","volume":"133","author":"Wilson","year":"1959","journal-title":"Anat. Rec."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00005-019-00552-7","article-title":"Role of macrophages in pregnancy and related complications","volume":"67","author":"Jena","year":"2019","journal-title":"Arch. Immunol. Exp."},{"key":"ref_29","first-page":"320","article-title":"Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates","volume":"7","author":"Medawar","year":"1953","journal-title":"Sym. Soc. Exp. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nri.2017.64","article-title":"The unique immunological and microbial aspects of pregnancy","volume":"17","author":"Mor","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/nm1452","article-title":"Decidual nk cells regulate key developmental processes at the human fetal-maternal interface","volume":"12","author":"Hanna","year":"2006","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1172\/JCI60561","article-title":"Macrophages regulate corpus luteum development during embryo implantation in mice","volume":"123","author":"Care","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_33","unstructured":"H\u00fcbschen, J.M., and Muller, C.P. (2018). Rubella and Congenital Rubella, Elsevier."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1128\/CMR.13.4.571","article-title":"Rubella virus replication and links to teratogenicity","volume":"13","author":"Lee","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1136\/jcp.29.Suppl_10.99","article-title":"Viral infections","volume":"10","author":"Dudgeon","year":"1976","journal-title":"J. Clin. Pathol. Suppl."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"123","DOI":"10.31486\/toj.18.0095","article-title":"Congenital cytomegalovirus infection","volume":"19","author":"Dietrich","year":"2019","journal-title":"Ochsner J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jcv.2007.09.004","article-title":"Congenital cytomegalovirus (cmv) infection as a cause of permanent bilateral hearing loss: A quantitative assessment","volume":"41","author":"Grosse","year":"2008","journal-title":"J. Clin. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e1985","DOI":"10.1002\/rmv.1985","article-title":"Congenital zika syndrome: Pitfalls in the placental barrier","volume":"28","author":"Robinson","year":"2018","journal-title":"Rev. Med. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/rmv.535","article-title":"Review and meta-analysis of the epidemiology of congenital cytomegalovirus (cmv) infection","volume":"17","author":"Kenneson","year":"2007","journal-title":"Rev. Med. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S912","DOI":"10.1093\/infdis\/jix431","article-title":"Pathogenesis of non-zika congenital viral infections","volume":"216","author":"Boppana","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.jcv.2011.07.005","article-title":"Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age","volume":"52","author":"Enders","year":"2011","journal-title":"J. Clin. Virol."},{"key":"ref_42","first-page":"1085","article-title":"Zika virus, french polynesia, south pacific, 2013","volume":"20","author":"Roche","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0140-6736(16)30902-3","article-title":"Congenital zika virus syndrome in brazil: A case series of the first 1501 livebirths with complete investigation","volume":"388","author":"Franca","year":"2016","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2807\/1560-7917.ES2014.19.13.20751","article-title":"Evidence of perinatal transmission of zika virus, french polynesia, december 2013 and february 2014","volume":"19","author":"Besnard","year":"2014","journal-title":"Eurosurveillance"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1056\/NEJMsr1604338","article-title":"Zika virus and birth defects--reviewing the evidence for causality","volume":"374","author":"Rasmussen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/uog.17404","article-title":"Association between zika virus and fetopathy: A prospective cohort study in french guiana","volume":"49","author":"Pomar","year":"2017","journal-title":"Ultrasound Obstet. Gynecol.: Off. J. Int. Soc. Ultrasound Obstet. Gynecol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.stem.2016.02.016","article-title":"Zika virus infects human cortical neural progenitors and attenuates their growth","volume":"18","author":"Tang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nm.4184","article-title":"Identification of small-molecule inhibitors of zika virus infection and induced neural cell death via a drug repurposing screen","volume":"22","author":"Xu","year":"2016","journal-title":"Nat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chowdhury, R., Allan, M.F., and Maranas, C.D. (2018). Optmaven-2.0: De novo design of variable antibody regions against targeted antigen epitopes. Antibodies, 7.","DOI":"10.3390\/antib7030023"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00430-015-0411-4","article-title":"Human cytomegalovirus: Taking the strain","volume":"204","author":"Wilkinson","year":"2015","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1093\/infdis\/jiz208","article-title":"Human cytomegalovirus genomes sequenced directly from clinical material: Variation, multiple-strain infection, recombination, and gene loss","volume":"220","author":"Suarez","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Dobbins, G.C., Patki, A., Chen, D., Tiwari, H.K., Hendrickson, C., Britt, W.J., Fowler, K., Chen, J.Y., Boppana, S.B., and Ross, S.A. (2019). Association of cmv genomic mutations with symptomatic infection and hearing loss in congenital cmv infection. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4681-0"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1080\/22221751.2019.1644967","article-title":"The african strain of zika virus causes more severe in utero infection than asian strain in a porcine fetal transmission model","volume":"8","author":"Udenze","year":"2019","journal-title":"Emerg Microbes Infec."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1126\/science.aam7120","article-title":"A single mutation in the prm protein of zika virus contributes to fetal microcephaly","volume":"358","author":"Yuan","year":"2017","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Esser-Nobis, K., Aarreberg, L.D., Roby, J.A., Fairgrieve, M.R., Green, R., and Gale, M. (2019). Comparative analysis of african and asian lineage-derived zika virus strains reveals differences in activation of and sensitivity to antiviral innate immunity. J. Virol., 93.","DOI":"10.1128\/JVI.00640-19"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e00934-18","DOI":"10.1128\/JVI.00934-18","article-title":"Rubella viruses shift cellular bioenergetics to a more oxidative and glycolytic phenotype with a strain-specific requirement for glutamine","volume":"92","author":"Bilz","year":"2018","journal-title":"J. Virol."},{"key":"ref_57","unstructured":"WHO (2013). Rubella virus nomenclature update: 2013. Wkly. Epidemiol. Rec., 88, 337\u2013343."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"587","DOI":"10.15585\/mmwr.mm6826a3","article-title":"Genetic characterization of measles and rubella viruses detected through global measles and rubella elimination surveillance, 2016-2018","volume":"68","author":"Brown","year":"2019","journal-title":"Mmwr. Morb. Mortal. Wkly. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1128\/JCM.02055-09","article-title":"Rubella virus genotypes in the people\u2019s republic of china between 1979 and 2007: A shift in endemic viruses during the 2001 rubella epidemic","volume":"48","author":"Zhu","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1128\/JCM.00181-10","article-title":"Phylogenetic analysis of rubella viruses involved in congenital rubella infections in france between 1995 and 2009","volume":"48","author":"Hubschen","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Martinez-Torres, A.O., Mosquera, M.M., De Ory, F., Gonzalez-Praetorius, A., and Echevarria, J.E. (2016). Genetic characterization of rubella virus strains detected in spain, 1998-2014. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162403"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"17982","DOI":"10.1038\/s41598-017-18281-2","article-title":"Progress towards rubella elimination after implementation of rubella immunization for over 20 years in shandong province, china","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12172","DOI":"10.1128\/JVI.01214-08","article-title":"Passive immunization reduces murine cytomegalovirus-induced brain pathology in newborn mice","volume":"82","author":"Cekinovic","year":"2008","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jcv.2007.10.008","article-title":"Comparison of vaccine strategies against congenital cmv infection in the guinea pig model","volume":"41","author":"Schleiss","year":"2008","journal-title":"J. Clin. Virol. : Off. Publ. Pan Am. Soc. Clin. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bradford, R.D., Yoo, Y.G., Golemac, M., Pugel, E.P., Jonjic, S., and Britt, W.J. (2015). Murine cmv-induced hearing loss is associated with inner ear inflammation and loss of spiral ganglia neurons. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004774"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/S0022-3476(97)70248-8","article-title":"Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection","volume":"130","author":"Fowler","year":"1997","journal-title":"J. Pediatrics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jcv.2005.09.016","article-title":"Congenital cytomegalovirus (cmv) infection and hearing deficit","volume":"35","author":"Fowler","year":"2006","journal-title":"J. Clin. Virol. : Off. Publ. Pan Am. Soc. Clin. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10424","DOI":"10.1523\/JNEUROSCI.0740-18.2018","article-title":"Congenital cytomegalovirus infection alters olfaction before hearing deterioration in mice","volume":"38","author":"Lazarini","year":"2018","journal-title":"J. Neurosci. : Off. J. Soc. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Marin-Lopez, A., Calvo-Pinilla, E., Moreno, S., Utrilla-Trigo, S., Nogales, A., Brun, A., Fikrig, E., and Ortego, J. (2019). Modeling arboviral infection in mice lacking the interferon alpha\/beta receptor. Viruses, 11.","DOI":"10.3390\/v11010035"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.4269\/ajtmh.16-0111","article-title":"Characterization of a novel murine model to study zika virus","volume":"94","author":"Rossi","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.chom.2016.05.009","article-title":"Zika virus targets human stat2 to inhibit type i interferon signaling","volume":"19","author":"Grant","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.chom.2018.04.003","article-title":"An immunocompetent mouse model of zika virus infection","volume":"23","author":"Gorman","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kim, I.J., Blackman, M.A., and Lin, J.S. (2019). Pre-clinical pregnancy models for evaluating zika vaccines. Trop. Med. Infect. Dis., 4.","DOI":"10.3390\/tropicalmed4020058"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Caine, E.A., Jagger, B.W., and Diamond, M.S. (2018). Animal models of zika virus infection during pregnancy. Viruses, 10.","DOI":"10.3390\/v10110598"},{"key":"ref_75","first-page":"390","article-title":"Experimental rubella virus infection in pregnant monkeys","volume":"110","author":"Parkman","year":"1965","journal-title":"Am. J. Dis. Child."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/0002-9378(67)90309-2","article-title":"Rubella-induced embryopathies in monkeys","volume":"99","author":"Delahunt","year":"1967","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1242\/dev.086165","article-title":"Human pluripotent stem cells: An emerging model in developmental biology","volume":"140","author":"Zhu","year":"2013","journal-title":"Development"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature13992","article-title":"A comparative encyclopedia of DNA elements in the mouse genome","volume":"515","author":"Yue","year":"2014","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1242\/dev.122820","article-title":"Enabling research with human embryonic and fetal tissue resources","volume":"142","author":"Gerrelli","year":"2015","journal-title":"Development"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1093\/hmg\/9.2.165","article-title":"Human-mouse differences in the embryonic expression patterns of developmental control genes and disease genes","volume":"9","author":"Fougerousse","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nature24033","article-title":"Genome editing reveals a role for oct4 in human embryogenesis","volume":"550","author":"Fogarty","year":"2017","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/ncb3347","article-title":"Self-organization of the human embryo in the absence of maternal tissues","volume":"18","author":"Shahbazi","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nature17948","article-title":"Self-organization of the in vitro attached human embryo","volume":"533","author":"Deglincerti","year":"2016","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12985-016-0679-z","article-title":"Tlr2 2258 g>a single nucleotide polymorphism and the risk of congenital infection with human cytomegalovirus","volume":"14","author":"Wujcicka","year":"2017","journal-title":"Virol. J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/joim.12829","article-title":"Variations in maternal adenylate cyclase genes are associated with congenital zika syndrome in a cohort from northeast, brazil","volume":"285","author":"Rossi","year":"2019","journal-title":"J. Intern. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1093\/infdis\/jiz392","article-title":"Association between zika virus microcephaly in newborns with the rs3775291 variant in toll-like receptor 3 and rs1799964 variant at tumor necrosis factor-alpha gene","volume":"220","author":"Santos","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41467-017-02790-9","article-title":"Discordant congenital zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells (vol 9, 2018)","volume":"9","author":"Caires","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.bpobgyn.2004.06.005","article-title":"Human embryonic stem cells as a model for early human development","volume":"18","author":"Dvash","year":"2004","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.addr.2018.05.005","article-title":"Stem cell-based retina models","volume":"140","author":"Achberger","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1002\/dvdy.24432","article-title":"Pluripotent stem cells as a model for embryonic patterning: From signaling dynamics to spatial organization in a dish","volume":"245","author":"Heemskerk","year":"2016","journal-title":"Dev. Dynam."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41586-019-1535-2","article-title":"Controlled modelling of human epiblast and amnion development using stem cells","volume":"573","author":"Zheng","year":"2019","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1126\/science.282.5391.1145","article-title":"Embryonic stem cell lines derived from human blastocysts","volume":"282","author":"Thomson","year":"1998","journal-title":"Science"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/nbt761","article-title":"Bmp4 initiates human embryonic stem cell differentiation to trophoblast","volume":"20","author":"Xu","year":"2002","journal-title":"Nat. Biotechnol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1242\/dev.092155","article-title":"Bmp4-directed trophoblast differentiation of human embryonic stem cells is mediated through delta np63(+) cytotrophoblast stem cell state","volume":"140","author":"Li","year":"2013","journal-title":"Development"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1126\/science.6322309","article-title":"Cytomegalovirus replicates in differentiated but not in undifferentiated human embryonal carcinoma cells","volume":"224","author":"Gonczol","year":"1984","journal-title":"Science"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1038\/sj.mt.6300251","article-title":"Functional analysis of various promoters in lentiviral vectors at different stages of in vitro differentiation of mouse embryonic stem cells","volume":"15","author":"Hong","year":"2007","journal-title":"Mol. Ther. : J. Am. Soc. Gene Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1089\/scd.2006.0088","article-title":"Efficiency of the elongation factor-1alpha promoter in mammalian embryonic stem cells using lentiviral gene delivery systems","volume":"16","author":"Kim","year":"2007","journal-title":"Stem Cells Dev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1089\/scd.2006.0057","article-title":"Transgenes delivered by lentiviral vector are suppressed in human embryonic stem cells in a promoter-dependent manner","volume":"16","author":"Xia","year":"2007","journal-title":"Stem Cells Dev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1089\/scd.2007.0084","article-title":"Promoter-dependent egfp expression during embryonic stem cell propagation and differentiation","volume":"17","author":"Wang","year":"2008","journal-title":"Stem Cells Dev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/bdra.20233","article-title":"Mouse embryonic stem cells are not susceptible to cytomegalovirus but acquire susceptibility during differentiation","volume":"76","author":"Matsukage","year":"2006","journal-title":"Birth Defects Res. Part. A Clin. Mol. Teratol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1128\/JVI.03492-13","article-title":"Human cytomegalovirus infection of human embryonic stem cell-derived primitive neural stem cells is restricted at several steps but leads to the persistence of viral DNA","volume":"88","author":"Belzile","year":"2014","journal-title":"J. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"D\u2019Aiuto, L., Di Maio, R., Heath, B., Raimondi, G., Milosevic, J., Watson, A.M., Bamne, M., Parks, W.T., Yang, L., and Lin, B. (2012). Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049700"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"11159","DOI":"10.1128\/JVI.01742-15","article-title":"Transition toward human cytomegalovirus susceptibility in early human embryonic stem cell-derived neural precursors","volume":"89","author":"Berger","year":"2015","journal-title":"J. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Brown, R.M., Rana, P., Jaeger, H.K., O\u2019Dowd, J.M., Balemba, O.B., and Fortunato, E.A. (2019). Human cytomegalovirus compromises development of cerebral organoids. J. Virol., 93.","DOI":"10.1128\/JVI.00957-19"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/NEN.0000000000000038","article-title":"Cytomegalovirus-induced brain malformations in fetuses","volume":"73","author":"Teissier","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Bilz, N.C., Willscher, E., Binder, H., Bohnke, J., Stanifer, M.L., Hubner, D., Boulant, S., Liebert, U.G., and Claus, C. (2019). Teratogenic rubella virus alters the endodermal differentiation capacity of human induced pluripotent stem cells. Cells, 8.","DOI":"10.3390\/cells8080870"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1038\/s41418-019-0324-7","article-title":"Protection of zikv infection-induced neuropathy by abrogation of acute antiviral response in human neural progenitors","volume":"26","author":"Liu","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.stem.2016.04.014","article-title":"Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor tlr3","volume":"19","author":"Dang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Salinas, S., Erkilic, N., Damodar, K., Moles, J.P., Fournier-Wirth, C., Van de Perre, P., Kalatzis, V., and Simonin, Y. (2017). Zika virus efficiently replicates in human retinal epithelium and disturbs its permeability. J. Virol., 91.","DOI":"10.1128\/JVI.02144-16"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ebiom.2018.12.010","article-title":"Zika virus induces strong inflammatory responses and impairs homeostasis and function of the human retinal pigment epithelium","volume":"39","author":"Simonin","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.stem.2019.11.016","article-title":"Zika virus targets glioblastoma stem cells through a sox2-integrin alphavbeta5 axis","volume":"26","author":"Zhu","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/(SICI)1097-0177(200004)217:4<327::AID-DVDY1>3.0.CO;2-K","article-title":"Endoderm and heart development","volume":"217","author":"Lough","year":"2000","journal-title":"Dev. Dyn. : Off. Publ. Am. Assoc. Anat."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1002\/sctm.18-0087","article-title":"Concise review: Molecular cytogenetics and quality control: Clinical guardians for pluripotent stem cells","volume":"7","author":"Rohani","year":"2018","journal-title":"Stem Cells Transl. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"13877","DOI":"10.1038\/s41598-018-31880-x","article-title":"Optimization of cell-laden bioinks for 3d bioprinting and efficient infection with influenza a virus","volume":"8","author":"Berg","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/d41586-018-05586-z","article-title":"The labs growing human embryos for longer than ever before","volume":"559","author":"Shen","year":"2018","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13059-018-1490-5","article-title":"A comparative study of endoderm differentiation in humans and chimpanzees","volume":"19","author":"Blake","year":"2018","journal-title":"Genome Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"E9579","DOI":"10.1073\/pnas.1708341114","article-title":"Gata2\/3-tfap2a\/c transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency","volume":"114","author":"Krendl","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/dvdy.24662","article-title":"Applications of human brain organoids to clinical problems","volume":"248","author":"Chen","year":"2019","journal-title":"Dev. Dyn. : Off. Publ. Am. Assoc. Anat."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.celrep.2017.09.047","article-title":"Self-organized cerebral organoids with human-specific features predict effective drugs to combat zika virus infection","volume":"21","author":"Watanabe","year":"2017","journal-title":"Cell Rep."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/3\/542\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:01:54Z","timestamp":1760173314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/3\/542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,26]]},"references-count":119,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["cells9030542"],"URL":"https:\/\/doi.org\/10.3390\/cells9030542","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,26]]}}}