Cells infected with human papilloma pseudovirus display nuclear reorganization and heterogenous infection kinetics

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buir.contributor.authorBarbier, Michaƫl
buir.contributor.orcidBarbier, Michaƫl|0000-0001-5155-4036
dc.citation.epage1048en_US
dc.citation.issueNumber12en_US
dc.citation.spage1035en_US
dc.citation.volumeNumber101en_US
dc.contributor.authorMolenberghs, F.
dc.contributor.authorVerschuuren, M.
dc.contributor.authorBogers, J. J.
dc.contributor.authorCools, N.
dc.contributor.authorDelputte, P.
dc.contributor.authorSchelhaas, M.
dc.contributor.authorBarbier, Michaƫl
dc.contributor.authorDe Vos, W.
dc.date.accessioned2023-02-16T07:16:21Z
dc.date.available2023-02-16T07:16:21Z
dc.date.issued2022-06-06
dc.description.abstractHuman papillomaviruses (HPV) are small, non-enveloped DNA viruses, which upon chronic infection can provoke cervical and head-and-neck cancers. Although the infectious life cycle of HPV has been studied and a vaccine is available for the most prevalent cancer-causing 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-content 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-resolved 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-based single cell analysis, we revealed phenotypic alterations that accompany HPV PsV infection in individual cells, and which may be relevant for therapeutic drug screens.en_US
dc.description.provenanceSubmitted by Aleyna Demirkıran (demirkiranaleyna99@gmail.com) on 2023-02-16T07:16:21Z No. of bitstreams: 1 Cells_infected_with_human_papilloma_pseudovirus_display_nuclear_reorganization_and_heterogenous_infection_kinetics.pdf: 3047354 bytes, checksum: ded386e9020b1fa4cb00c90f3d809eda (MD5)en
dc.description.provenanceMade available in DSpace on 2023-02-16T07:16:21Z (GMT). No. of bitstreams: 1 Cells_infected_with_human_papilloma_pseudovirus_display_nuclear_reorganization_and_heterogenous_infection_kinetics.pdf: 3047354 bytes, checksum: ded386e9020b1fa4cb00c90f3d809eda (MD5) Previous issue date: 2022-06-06en
dc.identifier.doi10.1002/cyto.a.24663en_US
dc.identifier.eissn1552-4930
dc.identifier.issn1552-4922
dc.identifier.urihttp://hdl.handle.net/11693/111392
dc.language.isoEnglishen_US
dc.publisherJohn Wiley & Sons, Ltden_US
dc.relation.isversionofhttps://www.doi.org/10.1002/cyto.a.24663en_US
dc.source.titleCytometryen_US
dc.subjectCell cycleen_US
dc.subjectHigh-throughput microscopyen_US
dc.subjectHuman papillomavirusen_US
dc.subjectInfection kineticsen_US
dc.subjectLive cell imagingen_US
dc.subjectNucleusen_US
dc.subjectPseudovirusen_US
dc.titleCells infected with human papilloma pseudovirus display nuclear reorganization and heterogenous infection kineticsen_US
dc.typeArticleen_US

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