GAP31 protein as the anti-EBV drugs to investigate anti-EB virus activity

• Main Authors: Wu, Hsuan-Hui, 吳宣慧
• Other Authors: Peng, Chih-Wen
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/04668111989987607107

碩士 === 慈濟大學 === 生命科學系碩士班 === 103 === Epstein-Barr virus (EBV) is one of the most common human viruses. It is also associated with several human malignancies. EBV established latent infection in B lymphocytes involved the activation of gene expression of six EBV nuclear antigens (EBNA) and three latency-associated membrane proteins. 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. EBNA1-dependent functions involve specific binding at the site of the latent origin of replication, oriP, which is composed of two cognate elements, the dyad symmetry (DS) and the family repeats (FR). Inhibitors that target EBNA1 binding to the oriP DNA may potentially terminate the persistency of the EBV latent infection and consequently abrogate the pathogenicity of EBV to cause malignancies or other diseases. GAP31 is a plant protein with a molecular weight by approximately 31kDa found in the seeds of Gelonium multiflorum, an ancient medicinal plant from the Himalayan Mountains. Cumulative evidence indicated that GAP31 exhibits potent antiviral activities through acting as a type I ribosome inhibitory protein (type-I RIP), DNA topoisomerase inhibitor, RNA N-glycosidase inhibitor, and HIV-1 integrase inhibitor. By far, the antiviral response of GAP31 has been reported as an antagonist for herpes simplex virus (HSV), HIV, and Hepatitis B virus (HBV), however, it remains unclear whether GAP31 can also target to EBV infection. In this study, we established an EBNA1/oriP based luciferase reporter assay platform to evaluate the anti-EBV activity of GAP31 by targeting to EBNA1/oirP. Furthermore, a series of functional and biochemical analyses were performed to further explore the antiviral activity of GAP31 on EBV. Our current findings suggested that GAP31 can prevent EBNA1 binding to oriP and ultimately debilitates episome maintenance and transcription. These data suggest that GAP31 has a potential anti-EBV activity, which may be develop as an ideal anti-EBV drug in the near future.