Epstein-Barr Virus and latent membrane protein 1 modulate host B cell microRNA to promote cell survival
Abstract/Contents
- Abstract
- Over 90% of humans are carriers for the B cell lymphotrophic [gamma]-herpes virus Epstein-Barr Virus (EBV). Though normally benign, EBV is the causative agent of infectious mononucleosis (IM) and is associated with multiple B cell malignancies, including post-transplant lymphoproliferative disease (PTLD). In immunodeficient and immune compromised individuals, proliferating EBV-infected B cells can progress to lymphoproliferative disease, transformation and malignancy due to the absence of a robust immune system to constrain the expansion of EBV-infected cells. Here we examine the expression of host cell microRNA in EBV-transformed B cells and following activation of the EBV viral oncogene latent membrane protein 1 (LMP1). We find that microRNA-194 is expressed at lower levels in EBV+ B lymphoma cell lines derived from patients with PTLD and that this microRNA is specifically suppressed by activation of tumor-derived LMP1 molecules. IL-10, required for autonomous growth of EBV-transformed B cells, is a direct target of microRNA-194. The overexpression of microRNA-194 in tumor-derived EBV-transformed B cells significantly decreased IL-10 production and significantly increased apoptosis. This phenotype was partially yet significantly rescued by the addition of exogenous IL-10. Thus, IL-10 expression, which acts as an autocrine growth factor for EBV+ B cell lymphomas, is promoted by EBV-induced suppression of microRNA-194.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Harris-Arnold, Aleishia Geraldine Christane |
|---|---|
| Associated with | Stanford University, Program in Immunology. |
| Primary advisor | Martinez, Olivia |
| Thesis advisor | Martinez, Olivia |
| Thesis advisor | Krams, Sheri Michele |
| Thesis advisor | Lewis, David |
| Thesis advisor | Mellins, Elizabeth |
| Advisor | Krams, Sheri Michele |
| Advisor | Lewis, David |
| Advisor | Mellins, Elizabeth |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Aleishia Geraldine Christane Harris-Arnold. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Aleishia Geraldine Christane Harris-Arnold
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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