{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:39:26Z","timestamp":1792528766258,"version":"4.5.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"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":["Virol J"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Human herpesvirus infections span a wide variety of pathogenic outcomes, with individual representatives comprising a huge clinical relevance on human health. Translational research efforts are directed towards the improvement of broadly applicable preventive measures and detailed understanding of viral pathogenesis. Here, we studied rate-limiting steps in viral replication that show high mechanistic conservation among the\n                    <jats:italic>Herpesviridae<\/jats:italic>\n                    family members, in particular concerning the viral nucleocytoplasmic capsid egress. As characterized for several herpesviruses, viral nuclear egress is facilitated by the virus-induced local nuclear lamina rearrangements of infected cells. Hereby, the virus-mediated site-specific phosphorylation at lamin A\/C Ser22, followed by\n                    <jats:italic>cis\/trans<\/jats:italic>\n                    isomerization of the structural conformation, leads to the induction of lamina-depleted areas (LDAs). We have generated an LDA reporter system in primary human fibroblasts (HFFs), which conditionally express the autofluorescent lamin A\/C-RFP fusion construct, for quantifying viral nuclear egress activity. This system was successfully applied for human and animal cytomegaloviruses as well as a selection of \u03b1-, \u03b2-, and \u03b3-herpesviruses shown here. Our results illustrate that (i) the reporter system was effective in a quantitative way for all viruses analyzed; (ii) the process of LDA formation showed consistency among herpesviruses; (iii) the impairment of viral kinase activity, responsible for lamin A\/C Ser22 phosphorylation, significantly reduced LDA formation; and (iv) inhibitory small molecules, directed either to the viral nuclear egress complex or the cellular isomerase activity, likewise provide an LDA-blocking effect leading to strong antiviral efficacy. Thus, the autofluorescent reporter cell model provides manifold options to study herpesviral productive replication, nuclear host interaction, and the pathogenesis-related impact of regulatory factors.\n                  <\/jats:p>","DOI":"10.1186\/s12985-026-03334-8","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:55:34Z","timestamp":1792464934000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Herpesviruses show consistency in their nuclear egress-associated induction of lamina-depleted areas as measured in an autofluorescent reporter cell model"],"prefix":"10.1186","volume":"23","author":[{"given":"Kishore","family":"Dhotre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Weghorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Sch\u00fctz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Marschall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"3334_CR1","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/323560a0","volume":"323","author":"U Aebi","year":"1986","unstructured":"Aebi U, Cohn J, Buhle L, Gerace L. The nuclear lamina is a meshwork of intermediate-type filaments. Nature. 1986;323:560\u20134.","journal-title":"Nature"},{"key":"3334_CR2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a040113","author":"X Wong","year":"2022","unstructured":"Wong X, Melendez-Perez AJ, Reddy KL. The nuclear lamina. Cold Spring Harb Perspect Biol. 2022. https:\/\/doi.org\/10.1101\/cshperspect.a040113.","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"3334_CR3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/bs.aivir.2015.10.002","volume":"94","author":"T Hellberg","year":"2016","unstructured":"Hellberg T, Pa\u00dfvogel L, Schulz KS, Klupp BG, Mettenleiter TC. Nuclear Egress of Herpesviruses: the Prototypic Vesicular Nucleocytoplasmic Transport. Adv Virus Res. 2016;94:81\u2013140.","journal-title":"Adv Virus Res"},{"key":"3334_CR4","volume":"14","author":"KS Keuenhof","year":"2023","unstructured":"Keuenhof KS, Kohler V, Broeskamp F, Panagaki D, Speese SD, B\u00fcttner S, et al. Nuclear envelope budding and its cellular functions. Nucleus (Calcutta). 2023;14:2178184.","journal-title":"Nucleus (Calcutta)"},{"key":"3334_CR5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/19491034.2016.1149665","volume":"7","author":"JB Bosse","year":"2016","unstructured":"Bosse JB, Enquist LW. The diffusive way out: herpesviruses remodel the host nucleus, enabling capsids to access the inner nuclear membrane. Nucleus (Calcutta). 2016;7:13\u20139.","journal-title":"Nucleus (Calcutta)"},{"key":"3334_CR6","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.1934","author":"M Marschall","year":"2017","unstructured":"Marschall M, Muller YA, Diewald B, Sticht H, Milbradt J. The human cytomegalovirus nuclear egress complex unites multiple functions: recruitment of effectors, nuclear envelope rearrangement, and docking to nuclear capsids. Rev Med Virol. 2017. https:\/\/doi.org\/10.1002\/rmv.1934.","journal-title":"Rev Med Virol"},{"key":"3334_CR7","doi-asserted-by":"crossref","first-page":"13979","DOI":"10.1074\/jbc.M109.063628","volume":"285","author":"J Milbradt","year":"2010","unstructured":"Milbradt J, Webel R, Auerochs S, Sticht H, Marschall M. Novel mode of phosphorylation-triggered reorganization of the nuclear lamina during nuclear egress of human cytomegalovirus. J Biol Chem. 2010;285:13979\u201389.","journal-title":"J Biol Chem"},{"key":"3334_CR8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005825","volume":"12","author":"J Milbradt","year":"2016","unstructured":"Milbradt J, Hutterer C, Bahsi H, Wagner S, Sonntag E, Horn AH, et al. The prolyl isomerase Pin1 promotes the herpesvirus-induced phosphorylation-dependent disassembly of the nuclear lamina required for nucleocytoplasmic egress. PLoS Pathog. 2016;12:e1005825.","journal-title":"PLoS Pathog"},{"key":"3334_CR9","doi-asserted-by":"crossref","unstructured":"Dhotre K, Sch\u00fctz M, von Essen S, Fortelny L, Wangen C, Hahn F, Sticht H, Marschall M. Conserved mode of nuclear lamina distortion by primate cytomegaloviruses: importance of the pSer22 motif, viral kinase and cis\/trans isomerase Pin1 activity. J Gen Virol. 2025;106.","DOI":"10.1099\/jgv.0.002160"},{"key":"3334_CR10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/1521654031000070645","volume":"55","author":"PE Boehmer","year":"2003","unstructured":"Boehmer PE, Nimonkar AV. Herpes virus replication. 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Have NEC coat, will travel: structural basis of membrane budding during nuclear egress in herpesviruses. Adv Virus Res. 2017;97:107\u201341.","journal-title":"Adv Virus Res"},{"key":"3334_CR17","doi-asserted-by":"publisher","DOI":"10.3390\/v13040702","author":"CP Lee","year":"2021","unstructured":"Lee CP, Chen MR. Conquering the nuclear envelope barriers by EBV lytic replication. Viruses. 2021. https:\/\/doi.org\/10.3390\/v13040702.","journal-title":"Viruses"},{"key":"3334_CR18","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ceb.2016.12.007","volume":"46","author":"MF Lye","year":"2017","unstructured":"Lye MF, Wilkie AR, Filman DJ, Hogle JM, Coen DM. Getting to and through the inner nuclear membrane during herpesvirus nuclear egress. 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