A Mouse Model to Study the Pathogenesis of γ-herpesviral Infections in Germinal Center B Cells
Autor: | Ursula Rambold, Stefanie Sperling, Zakir Chew, Yan Wang, Beatrix Steer, Krisztina Zeller, Lothar J. Strobl, Ursula Zimber-Strobl, Heiko Adler |
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Jazyk: | angličtina |
Rok vydání: | 2023 |
Předmět: | |
Zdroj: | Cells, Vol 12, Iss 24, p 2780 (2023) |
Druh dokumentu: | article |
ISSN: | 12242780 2073-4409 |
DOI: | 10.3390/cells12242780 |
Popis: | 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. |
Databáze: | Directory of Open Access Journals |
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