{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T14:44:20Z","timestamp":1769525060041,"version":"3.49.0"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70113859"],"award-info":[{"award-number":["70113859"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsches Zentrum f\u00fcr Lungenforschung (DZL)","award":["70113859"],"award-info":[{"award-number":["70113859"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>CD30-positive germinal center (GC)-derived B cell lymphomas are frequently linked to Epstein\u2013Barr Virus (EBV) infection. However, a suitable animal model for the investigation of the interplay between \u03b3-herpesvirus and host cells in B cell pathogenesis is currently lacking. Here, we present a novel in vivo model enabling the analysis of genetically modified viruses in combination with genetically modified GC B cells. As a murine \u03b3-herpesvirus, we used MHV-68 closely mirroring the biology of EBV. Our key finding was that Cre-mediated recombination can be successfully induced by an MHV-68 infection in GC B cells from C\u03b31-Cre mice allowing for deletion or activation of loxP-flanked cellular genes. The implementation of PrimeFlow RNA assay for MHV-68 demonstrated the enrichment of MHV-68 in GC and isotype-switched B cells. As illustrations of virus and cellular modifications, we inserted the EBV gene LMP2A into the MHV-68 genome and induced constitutively active CD30-signaling in GC B cells through MHV-68 infections, respectively. While the LMP2A-expressing MHV-68 behaved similarly to wildtype MHV-68, virally induced constitutively active CD30-signaling in GC B cells led to the expansion of a pre-plasmablastic population. The findings underscore the potential of our novel tools to address crucial questions about the interaction between herpesviral infections and deregulated cellular gene-expression in future studies.<\/jats:p>","DOI":"10.3390\/cells12242780","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T11:32:29Z","timestamp":1701862349000},"page":"2780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Mouse Model to Study the Pathogenesis of \u03b3-herpesviral Infections in Germinal Center B Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7112-0749","authenticated-orcid":false,"given":"Ursula","family":"Rambold","sequence":"first","affiliation":[{"name":"Institute of Asthma and Allergy Prevention, Helmholtz Center Munich, German Research Center for Environmental Health, Member of the German Center of Lung Research (DZL), 85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Sperling","sequence":"additional","affiliation":[{"name":"Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7187-4890","authenticated-orcid":false,"given":"Zakir","family":"Chew","sequence":"additional","affiliation":[{"name":"Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrix","family":"Steer","sequence":"additional","affiliation":[{"name":"Institute of Asthma and Allergy Prevention, Helmholtz Center Munich, German Research Center for Environmental Health, Member of the German Center of Lung Research (DZL), 85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krisztina","family":"Zeller","sequence":"additional","affiliation":[{"name":"Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-1862","authenticated-orcid":false,"given":"Lothar J.","family":"Strobl","sequence":"additional","affiliation":[{"name":"Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, 81377 Munich, Germany"},{"name":"Institute of Lung Health and Immunity, Helmholtz Center Munich, German Research Center for Environmental Health, Member of the German Center of Lung Research (DZL), 85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9765-5251","authenticated-orcid":false,"given":"Ursula","family":"Zimber-Strobl","sequence":"additional","affiliation":[{"name":"Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, 81377 Munich, Germany"},{"name":"Institute of Lung Health and Immunity, Helmholtz Center Munich, German Research Center for Environmental Health, Member of the German Center of Lung Research (DZL), 85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6481-6709","authenticated-orcid":false,"given":"Heiko","family":"Adler","sequence":"additional","affiliation":[{"name":"Institute of Asthma and Allergy Prevention, Helmholtz Center Munich, German Research Center for Environmental Health, Member of the German Center of Lung Research (DZL), 85764 Neuherberg, Germany"},{"name":"Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-University Munich, Member of the German Center of Lung Research (DZL), 80336 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"B\u00f6ni, M., Rieble, L., and M\u00fcnz, C. 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