Epstein-Barr virus lytic replication and the mTOR pathway

Epstein-Barr virus (EBV), a member of the Herpesviridae family, is a widespread pathogen that is associated with a variety of diseases, including infectious mononucleosis, several types of cancers, and multiple sclerosis. Due to its potential health-related effects, it is important to study this virus at the molecular level, including how EBV viral proteins interact with, both directly and indirectly, cellular proteins, especially cellular proteins whose functions are known to be associated with diseases such as cancer.  Our long term goal for this line of research is to discover and study important viral/cellular protein interactions, with the hope to manipulate these interactions to prevent viral replication.

With this research we aim to investigate the interaction of mTOR pathway-related proteins with the EBV lytic cycle. mTOR (mechanistic target of rapamycin) is a kinase at the heart of a major signaling pathway. Extracellular signals such as various nutrient levels and growth factors impinge on the mTOR pathway to control a variety of processes including protein translation, autophagy, cell growth, and mitochondrial metabolism.  We previously found that the inhibition of mTOR was sufficient to reduce EBV lytic replication in B cells, while having the opposite effect in epithelial cells. (1) By determining how the mTOR pathway and EBV intersect, we will gain insight into the consequences of giving mTOR inhibitors to patients for immunosuppressive or anti-cancer applications, in relation to EBV infection status.

  1. Adamson, A., B. Le, and B. Siedenburg. 2014. Inhibition of mTOR inhibits lytic replication of Epstein-Barr virus in a cell-type specific manner. Virology Journal 11:110.

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