Endemic Burkitt lymphoma, Epstein Barr virus, transcriptome, somatic mutations Abstract Endemic Burkitt lymphoma eBL is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus EBVunlike sporadic Burkitt Lymphoma sBL that occurs with a lower incidence in developed countries. Despite this increased burden the study of eBL has lagged. Additionally, while EBV was isolated from an African Burkitt lymphoma tumor 50 years ago, however, the impact of viral variation in oncogenesis is just beginning to be fully explored.
Like other herpesviruses, EBV has a biphasic infection cycle which includes latent and lytic programs. Upon primary infection, the virus establishes a lifelong latency in memory B lymphocytes characterized by a highly restricted gene expression and lack of virion production.
Signals responsible for differentiation of mature B lymphocytes into plasma cells may activate viral lytic program in latently infected cells leading to a coordinated expression of majority of viral genes and production of progeny virions.
Although most infections are asymptomatic, the primary clinical manifestation of EBV infection is infectious mononucleosis IMwhich accounts forcases each year in the US.
Cellular protein kinases have been reported to play a role in the viral life cycle, but their influence on different stages of EBV life cycle has not been studied extensively.
Therefore, in the first part of my dissertation, I investigated the involvement of cellular protein kinases in the EBV lytic program.
To this end, signaling pathways mediating Epstein-Barr virus EBV reactivation by antigen-bound B-cell receptor BCR were analyzed using a panel of 80 protein kinase inhibitors.
Broad range protein kinase inhibitors Staurosporin, KA, and PKC significantly reduced the EBV genome copy numbers measured 48 hours after reactivation, perhaps due to their higher toxicity. None of the tested compounds, except for KA, affected the activity of the EBV-encoded protein kinase in vitro.
The goal of the second part of my dissertation was to comprehensively characterize IgG response to EBV infection in humans. Currently, EBV serology is used to confirm the EBV infection status of a patient, but there are no clinical markers available to date to diagnose EBV-associated cancers.
Antibodies against two of these antigens, VCA and NA, are produced by almost all EBV carriers for their entire lifetime, and therefore, detection of these antibodies makes it impossible to differentiate between EBV carriers and EBV-associated cancer patients.
To address this deficiency, the current project sought to determine if the human antibody response to EBV significantly differed between asymptomatic EBV carriers versus EBV-associated cancer patients. In addition, I have confirmed previous observations that the antibody response in sera from EBV-associated NPC patients differs significantly from that in sera from EBV seropositive individuals who did not develop an EBV-associated malignancy.
These data advocate the feasibility of developing a serological assay that may be able to diagnose EBV-associated malignancies at early stages of the disease.
Moreover, further studies are warranted to explore the prognostic value of such biomarkers, which could identify individuals prone to developing EBV-associated malignancies, allow their close monitoring, and early intervention.Dissertations-ebv and lymphoma.
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Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus (EBV), unlike sporadic Burkitt Lymphoma (sBL) that occurs with a lower incidence in developed countries.
Despite this increased burden the study of eBL has lagged. Additionally, while EBV was isolated from an African Burkitt lymphoma tumor 50 Author: Yasin Kaymaz. what was essays to do good about writing illustrative essay cell phones present essay compare contrast essay macbeth beowulf holiday themed writing paper clinching statement persuasive essay the academic essay major point in essay ontological argument against the existence of god essay keep rivers clean essay serving in florida analysis essay.
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