DNA Damage Response Suppresses Epstein-Barr Virus-Driven Proliferation of Primary Human B Cells

Loading...
Thumbnail Image

Date

2012

Advisors

Luftig, Micah A

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

421
views
781
downloads

Abstract

The interaction of human tumor viruses with host growth suppressive pathways is a fine balance between controlled latent infection and virus-induced oncogenesis. This dissertation elucidates how Epstein-Barr virus interacts with the host growth suppressive DNA damage response signaling pathways (DDR) in order to transform infected human B lymphocytes.

Here I report that the activation of the ATM/Chk2 branch of the DDR in hyper-proliferating infected B cells results in G1/S cell cycle arrest and limits viral-mediated transformation. Similar growth arrest was found in mitogen-driven proliferating of B cells that sets the DDR as a default growth suppressive mechanism in human B cells. Hence, the viral protein EBNA3C functions to attenuate the host DDR and to promote immortalization of a small portion of infected B cells. Additionally, the pharmacological inhibition of the DDR in vitro increases viral immortalization of memory B cells that facilitates the isolation of broadly neutralizing antibodies to various infectious agents. Overall, this work defines early EBV-infected hyper-proliferating B cells as a new stage in viral infection that determines subsequent viral-mediated tumorigenesis.

Description

Provenance

Citation

Citation

Nikitin, Pavel A. (2012). DNA Damage Response Suppresses Epstein-Barr Virus-Driven Proliferation of Primary Human B Cells. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/6183.

Collections


Dukes student scholarship is made available to the public using a Creative Commons Attribution / Non-commercial / No derivative (CC-BY-NC-ND) license.