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Impact of innate immunity in the induction of epstein-barr virus-associated B-cell transformation and tumor formation

English title Impact of innate immunity in the induction of epstein-barr virus-associated B-cell transformation and tumor formation
Applicant Nadal David
Number 114118
Funding scheme Project funding
Research institution Infektiologie Medizinische Klinik Universitäts-Kinderklinik Zürich
Institution of higher education University of Zurich - ZH
Main discipline Experimental Microbiology
Start/End 01.04.2007 - 31.03.2010
Approved amount 197'608.00
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Keywords (6)

epstein-barr virus; infection; innate immunity; toll-like receptor; lymphoproliferation; transformation

Lay Summary (English)

Lead
Lay summary
Lymphoma is one of the most frequent cancers, and the vast majority of cases are of B-cell origin. Several types of lymphoma are linked to the Epstein-Barr virus (EBV), a B-cell tropic g herpes virus that establishes persistent, usually asymptomatic infection in > 95% of humans. EBV transforms B-cells in vitro to lymphoblastoid cell lines, indicating EBV’s potential role in tumor formation in vivo. The switch of latent EBV infection to lytic replication results in death of the infected cell. While a wealth of data has been accumulated from EBV’s impact on host gene expression in vitro and ex vivo, the critical events following primary cellular EBV infection and during the process leading to EBV-induced transformation remain elusive. Recent data suggest that components of the innate immune system such as Toll-like receptor 9 (TLR9) may operate in the pathogenesis of lymphomas. The interplay between TLR9 signaling and EBV-induced transformation has not been explored.We hypothesize that triggering of TLR9 induces EBV-associated B-cell transformation and tumor formation. Thus, we aim to explore different ways of EBV inoculation to increase the in vitro EBV infection rate of B cells isolated ex vivo from human tonsils from EBV-negative donors to subsequently investigate the course of infection from shortly after cellular EBV invasion till transformation in a pure target cell population. The proposed project will elucidate the EBV and B-cellular prerequisites for increased EBV infection in vitro and establish tools for the subsequent study of molecular mechanisms of EBV gene expression and responses to TLR9 triggering or inhibition in in vitro and in vivo models and lymphoproliferative lesions from patients.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
135028 Susceptibility of memory B-cells from distinct tissues to infection and transformation by Epstein-Barr virus 01.07.2011 Project funding

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