Dorner
Fakultäten » Medizinische Fakultät » Kinderspital Zürich: Medizinische Klinik » Infektiologie, Abteilung » Prof. Dr. David Nadal » Dorner
Completed research project
| Title / Titel | Epstein-Barr virus is able to directly infect antigen-specific memory B cells in vivo, where it establishes life-long persistence | ||
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| Abstract (PDF, 14 KB) | |||
| Summary / Zusammenfassung | The human -herpesvirus Epstein-Barr virus (EBV) uses tonsils as the portal of entry and reservoir to establish life-long persistence in the memory B cell pool of the infected host and may periodically reactivate from latency to result in the production of new virions. EBV is associated to several B cell malignancies including Burkitt’s lymphoma, Hodgkin’s disease or post-transplant lymphoproliferative disease. The association of EBV to promote tumor formation in vivo is based on the observation, that EBV is able to immortalize B cells in vitro. Although there are models trying to explain the establishment of EBV persistence in vivo, there is only little known about the biology and the mechanisms of the infection of the different B cell subpopulations. Therefore, we want to investigate the hypothesis that EBV infects tonsillar memory B cells ex vivo with similar efficiency as their naïve counterparts. Using an improved inoculation protocol and a recombinant EBV (B95.8EBfaV-GFP) encoding enhanced green fluorescent protein (EGFP) enabled augmenting the number of infected cells ex vivo and rapid subsequent identification and isolation of EBV-infected B cell subsets. Memory B cells from tonsils were infected ex vivo at similar frequency as naïve B cells. Moreover, tonsillar memory B cells exhibited comparable EBV mRNA expression patterns and transformation as naïve B cells subsequent to ex vivo EBV infection. Next we will characterize the EBV infected memory B cells regarding to their antigen specificity and their fate upon antigenic stimulation. This study will give more insights into the mechanisms required for establishment of EBV latent infection in the human memory B cell pool and also answer important questions of the mechanisms of EBV-associated tumorigenesis. |
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| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Forschungskredit der Universität Zürich |
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| Duration of Project / Projektdauer | Nov 2007 to May 2009 |