论文题目: | PTD-fused p53 as a potential antiviral agent directly suppresses HBV transcription and expression |
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作者: | Chu Xiaoyu, Wu Bo, Fan Hongxia, Hou Junwei, Hao Junli, Hu Jun, Wang Baozhong, Liu Guangze*, Li Changfei*, and Meng Songdong*. |
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刊物名称: | Antiviral Res |
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年份: | 2016 |
影响因子: | 3.788 |
论文下载: | http://www.sciencedirect.com/science/article/pii/S0166354216300109 |
摘要: | In Hepatitis B virus (HBV) infection, the virus generates numerous viral mRNAs/proteins and viral loads, which plays a major role in driving T cell tolerance, viral persistence, and hepatocellular carcinoma. However, currently available anti-HBV agents have no direct effect on viral mRNA transcription and protein expression. In this study, we designed a recombinant fusion of p53 protein with the cell-penetrating peptide PTD (protein transduction domain of trans-activator of transcription), which mediated p53 internalization into hepatocytes.PTD-p53 effectively suppressed HBV transcription and antigen expression by interaction with viral enhancers. We further provide evidence that PTD-p53 counteracts the viral transcription feedback loop and effectively suppressed HBV production of viral mRNAs, as well as HBsAg, HBeAg, and HBcAg, both in vitro and in vivo. Our results thereby provide a basis for developing a new therapeutic approach against HBV infection. |
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