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Open Access Highly Accessed Research

Inhibition of mTORC1 inhibits lytic replication of Epstein-Barr virus in a cell-type specific manner

Amy L Adamson*, Brandi T Le and Brian D Siedenburg

Author Affiliations

Department of Biology, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, USA

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Virology Journal 2014, 11:110  doi:10.1186/1743-422X-11-110

Published: 11 June 2014

Abstract

Background

Epstein-Barr virus is a human herpesvirus that infects a majority of the human population. Primary infection of Epstein-Barr virus (EBV) causes the syndrome infectious mononucleosis. This virus is also associated with several cancers, including Burkitt’s lymphoma, post-transplant lymphoproliferative disorder and nasopharyngeal carcinoma. As all herpesvirus family members, EBV initially replicates lytically to produce abundant virus particles, then enters a latent state to remain within the host indefinitely.

Methods

Through a genetic screen in Drosophila, we determined that reduction of Drosophila Tor activity altered EBV immediate-early protein function. To further investigate this finding, we inhibited mTOR in EBV-positive cells and investigated subsequent changes to lytic replication via Western blotting, flow cytometry, and quantitative PCR. The student T-test was used to evaluate significance.

Results

mTOR, the human homolog of Drosophila Tor, is an important protein at the center of a major signaling pathway that controls many aspects of cell biology. As the EBV immediate-early genes are responsible for EBV lytic replication, we examined the effect of inhibition of mTORC1 on EBV lytic replication in human EBV-positive cell lines. We determined that treatment of cells with rapamycin, which is an inhibitor of mTORC1 activity, led to a reduction in the ability of B cell lines to undergo lytic replication. In contrast, EBV-positive epithelial cell lines underwent higher levels of lytic replication when treated with rapamycin.

Conclusions

Overall, the responses of EBV-positive cell lines vary when treated with mTOR inhibitors, and this may be important when considering such inhibitors as anti-cancer therapeutic agents.

Keywords:
Epstein-Barr virus; BZLF1; BRLF1; Lytic replication; mTOR; Rapamycin