möglich sobald bei der ZB eingereicht worden ist.
A mouse model to study the pathogenesis of γ-herpesviral infections in germinal center B cells.
Cells 12:22 (2023)
CD30-positive germinal center (GC)-derived B cell lymphomas are frequently linked to Epstein-Barr Virus (EBV) infection. However, a suitable animal model for the investigation of the interplay between γ-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 γ-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 Cγ1-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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Cd30 ; Gc B Cells ; Lmp2a ; Mhv-68 ; Primeflow Rna Assay ; Conditional Transgenic Mice; Epstein-barr-virus; Membrane-protein 1; In-vivo; Mononucleosis; Expression; Routes; Memory
ISSN (print) / ISBN
2073-4409
e-ISSN
2073-4409
Zeitschrift
Cells
Quellenangaben
Band: 12,
Heft: 24,
Artikelnummer: 22
Verlag
MDPI
Verlagsort
Basel
Nichtpatentliteratur
Publikationen
Institut(e)
Institute of Asthma and Allergy Prevention (IAP)
Research Unit Gene Vector (AGV)
Lung Health and Immunity (LHI)
Research Unit Gene Vector (AGV)
Lung Health and Immunity (LHI)
Förderungen
Deutsche Krebshilfe