1. Epstein-Barr virus lytic replication activates and is dependent upon MAPK-interacting kinase 1/2 in a cell-type dependent manner.
- Author
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Adamson, Amy L., Jeffus, Dana, Davis, Alexis, and Greengrove, Eva
- Subjects
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EPSTEIN-Barr virus , *VIRAL replication , *CELL migration , *EPITHELIAL cells , *B cells - Abstract
Epstein-Barr virus (EBV) is known to manipulate its cellular environment to enhance viral replication, which can lead to dysregulation of cellular machinery, setting the stage for potential future disease. Previous research showed that under rapamycin-mediated inhibition of mTORC1, EBV lytic protein production was altered in a cell-type specific manner, suggesting that EBV differentially activates or utilizes signaling pathways in B versus epithelial cells. Here we correlated activation of the mTORC1, ERK1/2, and p38 pathways in relation to EBV lytic replication and discovered that activation of MAPK-interacting kinase 1/2 (Mnk1/2) was strongly associated with EBV lytic replication. Inhibition studies revealed that Mnk1/2 activated lytic replication in epithelial cells yet acted as an inhibitor of lytic replication in B cells. The ability of lytic epithelial cells to migrate, a potentially important aspect of metastasis, was also demonstrated to be dependent upon Mnk1/2 activity. • EBV lytic replication triggers activation of cellular Mnk, further promoting EBV lytic replication within epithelial cells. • Mnk stimulates the cell migration capability of lytic Epstein-Barr virus-positive epithelial cells. • Treatment of EBV-positive cells with rapamycin induces Mnk, in turn elevating lytic replication and migration of these cells. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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