Yin-Yang 1 regulation of Epstein-Barr virus BRLF1 transcription is altered during mTORC1 inhibition in a cell type-specific manner

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Steven Javier Moran (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Amy Adamson

Abstract: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that infects individuals worldwide. EBV actively replicates and establishes a latent infection in epithelial cells and B cells, which can lead to diseases such as infectious mononucleosis and Burkitt’s lymphoma. The reactivation of EBV from latency is contingent upon the expression of immediate-early genes BZLF1 and BRLF1. During EBV latency, BZLF1 and BRLF1 are negatively regulated by Yin-Yang 1 (YY1). YY1 is a highly expressed protein that participates in various cellular and viral processes. It has been demonstrated that the effects of rapamycin, a mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, on YY1 in epithelial cells and B cells alters EBV lytic replication. Rapamycin’s effects on YY1 cause it to positively regulate BZLF1 in epithelial cells and negatively regulate BZLF1 in B cells. While the effects of rapamycin on YY1 regulation of BZLF1 have been studied, the effects on BRLF1 have not. For this study, I investigated the effects of rapamycin on YY1 regulation of BRLF1 in epithelial cells and B cells during lytic replication. I wanted to determine if the effects of rapamycin on YY1 regulation of BRLF1 would be like the effects of rapamycin on YY1 regulation of BZLF1. The results of this study show that they are indeed similar. YY1 positively regulates BRLF1 in epithelial cells and negatively regulates BRLF1 in B cells during mTORC1 inhibition and lytic replication. This suggests that rapamycin alters YY1 transcriptional regulation of BRLF1 in a cell type-specific manner. Using rapamycin in combination with YY1-targeted therapies could reduce EBV infectivity and decrease the likelihood of developing EBV-associated diseases.

Additional Information

Publication
Thesis
Language: English
Date: 2018
Keywords
BRLF1, EBV, mTORC1, Rapamycin, Transcription, YY1
Subjects
Epstein-Barr virus
Epithelial cells
Rapamycin
Genetic transcription

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