{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:51:50Z","timestamp":1747147910091,"version":"3.40.5"},"reference-count":54,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T00:00:00Z","timestamp":1655510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["FWO 1152918N","FWO G005819N","FWO I003420N","FWO IRI I000321N"],"award-info":[{"award-number":["FWO 1152918N","FWO G005819N","FWO I003420N","FWO IRI I000321N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007660","name":"Universiteit Antwerpen","doi-asserted-by":"publisher","award":["BOF IMARK","IOF FFI210242","muNEURO"],"award-info":[{"award-number":["BOF IMARK","IOF FFI210242","muNEURO"]}],"id":[{"id":"10.13039\/501100007660","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Pt A"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human papillomaviruses (HPV) are small, non\u2010enveloped DNA viruses, which upon chronic infection can provoke cervical and head\u2010and\u2010neck cancers. Although the infectious life cycle of HPV has been studied and a vaccine is available for the most prevalent cancer\u2010causing HPV types, there are no antiviral agents to treat infected patients. Hence, there is a need for novel therapeutic entry points and a means to identify them. In this work, we have used high\u2010content microscopy to quantitatively investigate the early phase of HPV infection. Human cervical cancer cells and immortalized keratinocytes were exposed to pseudoviruses (PsV) of the widespread HPV type 16, in which the viral genome was replaced by a pseudogenome encoding a fluorescent reporter protein. Using the fluorescent signal as readout, we measured differences in infection between cell lines, which directly correlated with host cell proliferation rate. Parallel multiparametric analysis of nuclear organization revealed that HPV PsV infection alters nuclear organization and inflates promyelocytic leukemia protein body content, positioning these events at the early stage of HPV infection, upstream of viral replication. Time\u2010resolved analysis revealed a marked heterogeneity in infection kinetics even between two daughter cells, which we attribute to differences in viral load. Consistent with the requirement for mitotic nuclear envelope breakdown, pharmacological inhibition of the cell cycle dramatically blunted infection efficiency. Thus, by systematic image\u2010based single cell analysis, we revealed phenotypic alterations that accompany HPV PsV infection in individual cells, and which may be relevant for therapeutic drug screens.<\/jats:p>","DOI":"10.1002\/cyto.a.24663","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T03:53:53Z","timestamp":1654574033000},"page":"1035-1048","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cells infected with human papilloma pseudovirus display nuclear reorganization and heterogenous infection kinetics"],"prefix":"10.1002","volume":"101","author":[{"given":"Freya","family":"Molenberghs","sequence":"first","affiliation":[{"name":"Laboratory of Cell Biology and Histology, Department of Veterinary Sciences and Health Sciences University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlies","family":"Verschuuren","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology and Histology, Department of Veterinary Sciences and Health Sciences University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u00ebl","family":"Barbier","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology and Histology, Department of Veterinary Sciences and Health Sciences University of Antwerp Antwerp Belgium"},{"name":"Simply Complex Lab, UNAM Bilkent University Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes J.","family":"Bogers","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology and Histology, Department of Veterinary Sciences and Health Sciences University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Cools","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hematology, Faculty Medicine and Health Sciences University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Delputte","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene, Department of Biomedical Sciences University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Schelhaas","sequence":"additional","affiliation":[{"name":"Institute of Cellular Virology University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0960-6781","authenticated-orcid":false,"given":"Winnok H.","family":"De Vos","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology and Histology, Department of Veterinary Sciences and Health Sciences University of Antwerp Antwerp Belgium"},{"name":"Antwerp Centre for Advanced Microscopy (ACAM), University of Antwerp Antwerp Belgium"},{"name":"\u03bcNEURO Research Centre of Excellence, University of Antwerp Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.06.083"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02726-07"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094823"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00057-06"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2020.105875"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004162"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000318"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00454-19"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600638113"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007590"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404229101"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.112.24.4581"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00035"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2013.11.002"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.11.039"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2017.09.008"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.2.751-757.2004"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.5.2839-2846.2005"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471143030.cb2601s37"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72027-1"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.3.761"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020069"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1598"},{"key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/978-1-4939-2013-6_24","volume-title":"Cervical 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