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Rambold, U. ; Sperling, S. ; Chew, Z. ; Wang, Y. ; Steer, B. ; Zeller, K. ; Strobl, L.J. ; Zimber-Strobl, U. ; Adler, H.

A mouse model to study the pathogenesis of γ-herpesviral infections in germinal center B cells.

Cells 12:22 (2023)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords 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

Journal Cells

Quellenangaben Volume: 12, Issue: 24, Article Number: 22

Publisher MDPI

Publishing Place Basel

Non-patent literature Publications

Institute(s) Institute of Asthma and Allergy Prevention (IAP)
Research Unit Gene Vector (AGV)
Lung Health and Immunity (LHI)

Grants Deutsche Krebshilfe