(-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus lytic replication involves latent membrane protein 1-mediated MAPK signaling pathways

Li, H.; Luo, X.; Hu, J.; Liu, S.; Li, N.; Tang, M.; Weng, X.; Yi, W.; Gao, J.; Bode, A.; Dong, Z.; Cao, Y.

doi:10.1101/383497

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bioRxiv · 10.1101/383497

(-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus lytic replication involves latent membrane protein 1-mediated MAPK signaling pathways

Li, H.·Luo, X.·Hu, J.·Liu, S.·Li, N.·Tang, M.·Weng, X.·Yi, W.·Gao, J.·Bode, A.·Dong, Z.·Cao, Y.

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Abstract

AbstractEBV lytic replication has been shown to be important for carcinogenesis. Latent membrane protein 1 (LMP1) plays an important role in the viral latent infection and is abundantly expressed after EBV entry into the lytic cycle. However, the biological significance of LMP1 continuous expression in EBV lytic cycle is still not completely understood. We found that LMP1 promotes EBV reactivation by activating the downstream MAPK signaling in both AGS-EBV and B95.8 cells. In AGS-EBV cells, LMP1 induces EBV the initiation of the EBV lytic cycle in a p53 dependent manner. Activation of c-Jun by LMP1 through JNKs appears to be involved in EBV reactivation in p53 mutant B95.8 cells. We also demonstrated that EGCG, an anti-EBV agent, inhibits LMP1 expression and the activation of the downstream MAPK signaling pathways, followed by downregulation of EBV lytic protein expression level. Together, this study provides the first evidence that LMP1 promotes EBV reactivation via activation of the MAPK signaling pathways. Our findings further demonstrate that the mechanisms underlying EGCG inhibition of the EBV lytic replication involve the suppression of LMP1-mediated MAPK signaling pathways.\n\nSummary statementThis study definitely confirms the role of LMP1 in EBV reactivation and further explores the mechanism by which EGCG inhibits EBV lytic replication.

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Li, H., Luo, X., Hu, J., Liu, S., Li, N., Tang, M., Weng, X., Yi, W., Gao, J., Bode, A., Dong, Z., Cao, Y.. 2018-08-02. (-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus lytic replication involves latent membrane protein 1-mediated MAPK signaling pathways. https://doi.org/10.1101/383497

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