Berger
Fakultäten » Medizinische Fakultät » Kinderspital Zürich: Medizinische Klinik » Infektiologie, Abteilung » Prof. Dr. David Nadal » Berger
Completed research project
| Title / Titel | The level of viral LMP2A expression (in relation to its isoform LMP2B) is critical for activation of the lytic infection program and termination of tumor-promoting EBV latency | ||||||
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| Abstract (PDF, 14 KB) | |||||||
| Summary / Zusammenfassung | In this project we investigate the hypothesis that the quantitative level of latent mebrane protein (LMP)2A expression inversely correlates with the level and the potential to induce lytic Epstein-Barr virus (EBV) infection. While low level expression might be sufficient to mimic block B cell receptor (BCR) signaling, higher levels are needed to BCR-mediated signaling, including the induction of lytic infection. For these functions the expression level of LMP2A is dependent on that one of LMP2B exerting a dominant negative effect on LMP2A. We will test this hypothesis by extending our real-time PCR system for quantification of EBV gene expression with assays specifically detecting expression levels of LMP2A and LMP2B, respectively. These assays will allow to analyze LMP2A and LMP2B expression levels in EBV-infected lymphocytes and tumor cells, where we found different EBV gene expression patterns, and to correlate them with lytic gene expression. In addition, induction of lytic infection upon chemical stimulation with phorbol esters and BCR stimulation with surface immunglobulin crossliniking in our different cell lines will reveal a critical LMP2A (and LMP2B) expression level to block BCR-mediated signaling. These results are essential to evaluate future targets for treatment including, first, blocking of LMP2B to interrupt latent EBV-promoted proliferation eventually resulting in tumor formation, and second, a block of LMP2A to stop BCR-mediated proliferation and to induce lytic infection, eventually resulting in death instead of uncontrolled proliferation of the EBV-infected cell. |
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| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Foundation Krebsliga Kanton Zürich |
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| Duration of Project / Projektdauer | Aug 2004 to Jan 2006 |