title: PTD-fused p53 as a potential antiviral agent directly suppresses HBV transcription and expression.
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.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China; School of Life Sciences, Anhui University, Hefei, PR China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China; School of Life Sciences, Anhui University, Hefei, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Fan
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hou
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.
authors.forename: Junli
authors.initials: J
authors.lastname: Hao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China; School of Life Sciences, Anhui University, Hefei, PR China.
authors.forename: Baozhong
authors.initials: B
authors.lastname: Wang
authors.affiliation: Transgenic Engineering Research Laboratory, Infectious Disease Center, 458th Hospital, Guangzhou, PR China. Electronic address: lgze68@163.com.
authors.forename: Guangze
authors.initials: G
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China. Electronic address: lichangfei2006@163.com.
authors.forename: Changfei
authors.initials: C
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China. Electronic address: mengsd@im.ac.cn.
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004279:DNA, Viral / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D057846:Cell-Penetrating Peptides; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D012333:RNA, Messenger; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53
keywords: Antiviral; HBV; PTD; p53