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Nadal

Fakultäten » Medizinische Fakultät » Kinderspital Zürich: Medizinische Klinik » Infektiologie, Abteilung » Prof. Dr. David Nadal » Nadal

Completed research project

Title / Titel Impact of the innate immunity on EBV-associated B-cell transformation and tumor formation
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung We hypothesize that triggering of TLR9 induces EBV-associated B-cell transformation and tumor formation. Thus, we intend to explore different EBV inoculation methods to improve the in vitro EBV infection rate of B-cells purified ex vivo from human palatine tonsils from EBV-seronegative donors to subsequently investigate the course of EBV infection from shortly after cellular invasion till transformation in a pure target cell population. The use of a transformation competent EBV with a reporter gene expressing enhanced green fluorescent protein will enable us to sort and characterize the EBV-infected B-cells by flowcytometry. Thereby we will determine the efficiency of EBV infection in B-cells and their naïve and memory subpopulations purified using magnetic beads and investigate the role of the cellular EBV inoculum on survival, differentiation, proliferation, and transformation of infected cells by flowcytometry and in-house quantitative DNA polymerase chain reaction (PCR) assays. Building on the established in vitro tool, we aim to elucidate the gene expression behavior of EBV and the effects on B-cell survival, proliferation, differentiation, and transformation in response to signals from TLR9. The molecular events following primary EBV infection with or without triggering of TLR9 will be longitudinally recorded and quantified using in-house PCR assays, Western blot analysis and immunofluorescence microscopy targeting EBV genes.
Keywords / Suchbegriffe Epstein-Barr virus, infection, lymphoma, transformation, innate immunity, Toll-like receptor 9, gene expression profiling
Project leadership and contacts /
Projektleitung und Kontakte
Prof. David Nadal (Project Leader) david.nadal@kispi.uzh.ch
Funding source(s) /
Unterstützt durch
Foundation
Wolfermann-Nägeli-StiftungOPO-Stiftung
Duration of Project / Projektdauer Nov 2005 to Oct 2006