EGCG debilitates the persistence of EBV latency by reducing the DNA binding potency of nuclear antigen 1.
Because the expression of EBNA1 is prevalent in all EBV-associated tumors, it has become one of the most attractive drug targets for the discovery of anti-EBV compounds. In a cell-based reporter system, EBNA1 consistently upregulated the transcription of an oriP-Luc mini-EBV episome by 6- to 8-fold. The treatment of cells with 50 μM EGCG effectively blocked the binding of EBNA1 to oriP-DNA both in vivo and in vitro, which led to the abrogation of EBNA1-dependent episome maintenance and transcriptional enhancement. Importantly, the anti-EBNA1 effects caused by EGCG ultimately impaired the persistence of EBV latent infection. Our data suggest that the inhibition of EBNA1 activity by EGCG could be a promising starting point for the development of new protocols for anti-EBV therapy.
Department of Life Sciences, Tzu-Chi University, Hualien, Taiwan.
Ya-Lin
YL
Chen
Hsing-Lyn
HL
Tsai
Chih-Wen
CW
Peng
D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018741:Replication Origin / Q000187:drug effects; D017735:Virus Latency / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D019309:Epstein-Barr Virus Nuclear Antigens; D002392:Catechin; D004247:DNA; C045651:epigallocatechin gallate; C417029:EBV-encoded nuclear antigen 1