PTD-fused p53 as a potential antiviral agent directly suppresses HBV transcription and expression

PTD-fused p53 as a potential antiviral agent directly suppresses HBV transcription and expression
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PTD 融合的 p53 作为潜在的抗病毒剂直接抑制 HBV 转录和表达。

DOI:
10.1016/j.antiviral.2016.01.008
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发表时间:
2016-03-01
期刊:
影响因子:
7.6
通讯作者:
Meng, Songdong
Meng, Songdong
中科院分区:
医学2区
文献类型:
--
作者:
Chu, Xiaoyu;Wu, Bo;Meng, Songdong

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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. (C) 2016 Elsevier B.V. All rights reserved.