Why does Epstein -Barr virus express a non-transforming, truncated form of its oncoprotein, LMP -1?

Kimberly Dawn Erickson, Purdue University

Abstract

Epstein-Barr virus (EBV) is a human herpesvirus that infects greater than 90% of the adult human population. EBV is the causative agent of infectious mononucleosis and is associated with a number of human lymphomas and carcinomas. EBV infects resting human B-cells and establishes a latent infection. Latently infected B-cells enter the cell cycle, proliferate indefinitely, and thus are immortal. The Latent Membrane Protein-1 (LMP-1) is one of eleven viral gene products, and the only viral oncoprotein, expressed during viral latency in vitro. LMP-1's expression is essential for EBV's ability to immortalize primary human B-cells in vitro. A second promoter activated during lytic replication lies within the LMP-1 gene. Its activation gives rise to a protein that is identical to LMP-1's major signaling domain. This protein is called lytic LMP-1 (lyLMP-1) due to its dramatic upregulation during EBV's lytic cycle. Interestingly, lyLMP-1 does not share any of LMP-1's known activities. I have investigated the question: why does EBV express a truncated, non-transforming form of its oncoprotein, LMP-1? I found that lyLMP-1 is a component of EBV's virion and may be important for early infection events. Furthermore, my results suggest the lyLMP-1 negatively regulates LMP-1 signaling. EBV isolated from tumors does not encode the lyLMP-1 initiating methionine and therefore do not express the lyLMP-1 protein. I hypothesize that there is a positive selection for virus strains that do not encode lyLMP-1 providing these virus-infected cells a growth advantage given appropriate conditions (i.e. immune suppression). I will present a model in which lyLMP-1 negatively affects LMP-1's transforming activity and contributes to the disruption of immortalization and progression of EBV's lytic cycle.

Degree

Ph.D.

Advisors

Martin, Purdue University.

Subject Area

Molecular biology

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