Abstract
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.
References
Dec 23, 1988·Cell·A D Frankel, C O Pabo
Feb 28, 1998·The EMBO Journal·A OriY Shaul
May 2, 2002·Molecular Cell·Koji OkamotoCarol Prives
Sep 13, 2002·Journal of Viral Hepatitis·Naazneen MoollaPatrick Arbuthnot
Apr 3, 2007·Oncogene·S P HussainC C Harris
Apr 18, 2008·Cell Cycle·Surinder M SoondAnastasis Stephanou
Jun 6, 2008·Journal of Virology·Kimberley A ZimmermanD Lorne J Tyrrell
Apr 24, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Maria Stella De MitriMauro Bernardi
Apr 20, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yun-Fan Liaw
Jul 28, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yun-Fan Liaw
Nov 23, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Saifeng WangSongdong Meng
Dec 14, 2011·Gut·Antonio Bertoletti, Carlo Ferrari
Oct 12, 2012·Journal of Virology·Junli HaoSongdong Meng
Oct 24, 2012·Journal of Gastroenterology·Tai-Chung Tseng, Jia-Horng Kao
Nov 15, 2012·Vaccine·Bao ZhaoSongdong Meng
Dec 12, 2012·Journal of Virology·Changfei LiSongdong Meng
Jan 11, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Geoffrey Dusheiko
Feb 23, 2013·World Journal of Gastroenterology : WJG·Hélène JeulinEvelyne Schvoerer
Feb 27, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christine I WooddellDavid L Lewis
Mar 1, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Peixiang LanZhigang Tian
May 8, 2013·The Journal of Biological Chemistry·Yanling WangXiang-Dong Fu
May 17, 2013·Journal of Virology·Yu ZhangSongdong Meng
Jun 12, 2013·Seminars in Liver Disease·Dieter Glebe, Corinna M Bremer
Jun 19, 2013·PloS One·Hongxia FanSongdong Meng
Aug 13, 2013·PloS One·Shijian ZhangGuang Yang
Apr 22, 2014·Journal of Immunological Methods·Li WangXiang Zhong Liu
Apr 29, 2014·FEBS Letters·Vladimir J N Bykov, Klas G Wiman
Jun 24, 2014·Lancet·Christian TrépoAnna Lok
Oct 14, 2014·World Journal of Gastroenterology : WJG·Chan Ran YouSeung Kew Yoon
Citations
Jan 6, 2018·Journal of Drug Targeting·Xue-Wei CaoFu-Jun Wang
Jun 18, 2019·The Journal of General Virology·Liyuan QianSongdong Meng
Jul 18, 2018·Biomolecules·Bénédicte NdebokoLucyna Cova
Mar 7, 2020·Pharmaceutics·Rebecca E Taylor, Maliha Zahid
Nov 17, 2017·Journal of Medical Virology·Yubin LiLiansheng Ling
Oct 26, 2021·Tissue Barriers·Idris Zubairu SadiqUmar Aliyu Umar