{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:42:12Z","timestamp":1789882932816,"version":"4.0.1"},"reference-count":64,"publisher":"The Royal Society","issue":"1773","license":[{"start":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T00:00:00Z","timestamp":1554681600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["#RGPIN-2015-03855"],"award-info":[{"award-number":["#RGPIN-2015-03855"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["355858-2008"],"award-info":[{"award-number":["355858-2008"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["435891-2013"],"award-info":[{"award-number":["435891-2013"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["454402-2014"],"award-info":[{"award-number":["454402-2014"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Phil. Trans. R. Soc. B"],"published-print":{"date-parts":[[2019,5,27]]},"abstract":"<jats:p>Persistent infection with oncogenic human papillomavirus (HPV) may lead to cancer in mucosal and skin tissue. Consequently, HPV must have developed strategies to escape host immune surveillance. Nevertheless, most HPV infections are cleared by the infected host. Our laboratory investigates Langerhans cells (LCs), acting at the interface between innate and adaptive immunity. We hypothesize that this first line of defence is vital for potential HPV elimination. As an alternative to animal models, we use smaller-scale epithelial organoids grown from human primary keratinocytes derived from various anatomical sites. This approach is amenable to large sample sizes\u2014an essential aspect for scientific rigour and statistical power. To evaluate LCs phenotypically and molecularly during the viral life cycle and onset of carcinogenesis, we have included an engineered myeloid cell line with the ability to acquire an LC phenotype. This model is accurately tailored for the crucial time-window of early virus elimination in a complex organism and will shed more light on our long-standing research question of how naturally occurring HPV variants influence disease development. It may also be applied to other microorganism\u2013host interaction research or enquiries of epithelium immunobiology. Finally, our continuously updated pathogen\u2013host analysis tool enables state-of-the-art bioinformatics analyses of next-generation sequencing data.<\/jats:p>\n                  <jats:p>This article is part of the theme issue \u2018Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2018.0288","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T03:06:13Z","timestamp":1554692773000},"page":"20180288","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["An epithelial organoid model with Langerhans cells for assessing virus-host interactions"],"prefix":"10.1098","volume":"374","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-5546","authenticated-orcid":true,"given":"Robert","family":"Jackson","sequence":"first","affiliation":[{"name":"Probe Development and Biomarker Exploration, Thunder Bay Regional Health Research Institute, 980 Oliver Road, Thunder Bay, Ontario, Canada P7B 6V4"},{"name":"Biotechnology Program, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario, Canada P7B 5E1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8182-3559","authenticated-orcid":true,"given":"Statton","family":"Eade","sequence":"additional","affiliation":[{"name":"Probe Development and Biomarker Exploration, Thunder Bay Regional Health Research Institute, 980 Oliver Road, Thunder Bay, Ontario, Canada P7B 6V4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8192-1837","authenticated-orcid":true,"given":"Ingeborg","family":"Zehbe","sequence":"additional","affiliation":[{"name":"Probe Development and Biomarker Exploration, Thunder Bay Regional Health Research Institute, 980 Oliver Road, Thunder Bay, Ontario, Canada P7B 6V4"},{"name":"Department of Biology, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario, Canada P7B 5E1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2019,4,8]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12539993"},{"key":"e_1_3_6_3_2","first-page":"167","article-title":"Altered expression of proliferation and differentiation markers in human papillomavirus 16 and 18 immortalized epithelial cells grown in organotypic culture","volume":"140","author":"Merrick DT","year":"1992","journal-title":"Am. J. Pathol."},{"key":"e_1_3_6_4_2","first-page":"4858","article-title":"Tetrasomy is induced by human papillomavirus type 18 E7 gene expression in keratinocyte raft cultures","volume":"61","author":"Southern SA","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_3_6_5_2","first-page":"e3668","article-title":"Generation of organotypic raft cultures from primary human keratinocytes","volume":"60","author":"Anacker D","year":"2012","journal-title":"J. Vis. Exp."},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3312"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(75)90183-X"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.3.1274"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7008197"},{"key":"e_1_3_6_10_2","first-page":"673","article-title":"Epithelial cells immortalized by human papillomaviruses have premalignant characteristics in organotypic culture","volume":"138","author":"Blanton RA","year":"1991","journal-title":"Am. J. Pathol."},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1323879"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.7.1131"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9868"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/488S2a"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vex027"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70096-8"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2017.07.007"},{"key":"e_1_3_6_18_2","first-page":"829","article-title":"Human papillomavirus 16 E6 variants are more prevalent in invasive cervical carcinoma than the prototype","volume":"58","author":"Zehbe I","year":"1998","journal-title":"Cancer Res."},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.93"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101540"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-016-3203-3"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004280050173"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65324-2"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.2.701"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2015.05.017"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc798"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/v10020080"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(85)90214-4"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2013.07.018"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01512-12"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000905"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.11.796"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.17.1325"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/0017896915580446"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36150-4"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2008.09.036"},{"key":"e_1_3_6_37_2","first-page":"1","volume-title":"Current topics in Microbiology and Immunology","author":"Rodrigues N","year":"2018"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.2174\/1874357901206010249"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2006.01.003"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/361082a0"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.05028-11"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/437041a"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1006646"},{"key":"e_1_3_6_44_2","first-page":"540850","article-title":"HPV infection: immunological aspects and their utility in future therapy","volume":"2013","author":"Deligeoroglou E","year":"2013","journal-title":"Infect. Dis. Obst. Gynecol."},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2013.06.020"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.07.025"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.15.8378-8385.2003"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e10-11-0879"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.11.001"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2016.40"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308615100"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1735109"},{"key":"e_1_3_6_54_2","doi-asserted-by":"crossref","first-page":"9.3.1","DOI":"10.1002\/0471142727.mb0903s62","article-title":"Transfection by electroporation","volume":"62","author":"Potter H","year":"2003","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5082\/5\/3\/035011"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00869.x"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0199761"},{"key":"e_1_3_6_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006846"},{"key":"e_1_3_6_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22946"},{"key":"e_1_3_6_60_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0206111"},{"key":"e_1_3_6_61_2","first-page":"423","article-title":"MUTZ-3 Langerhans cell maturation and CXCL12 independent migration in reconstructed human gingiva","volume":"33","author":"Kosten IJ","year":"2016","journal-title":"ALTEX"},{"key":"e_1_3_6_62_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/627125"},{"key":"e_1_3_6_63_2","first-page":"bty1003","article-title":"Pathogen-Host Analysis Tool (PHAT): an integrative platform to analyze next-generation sequencing data","author":"Gibb CM","year":"2018","journal-title":"Bioinformatics"},{"key":"e_1_3_6_64_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1976.10480949"},{"key":"e_1_3_6_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1712018114"}],"container-title":["Philosophical Transactions of the Royal Society B: Biological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.2018.0288","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rstb.2018.0288","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.2018.0288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:20:55Z","timestamp":1778620855000},"score":1,"resource":{"primary":{"URL":"http:\/\/royalsocietypublishing.org\/rstb\/article\/42321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,8]]},"references-count":64,"journal-issue":{"issue":"1773","published-print":{"date-parts":[[2019,5,27]]}},"alternative-id":["10.1098\/rstb.2018.0288"],"URL":"https:\/\/doi.org\/10.1098\/rstb.2018.0288","relation":{},"ISSN":["0962-8436","1471-2970"],"issn-type":[{"value":"0962-8436","type":"print"},{"value":"1471-2970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,8]]},"assertion":[{"value":"2018-11-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}