Open AccessA peptide-based inhibitor of gp96 suppresses HBsAg expression and HBV replication by upregulation of p53
Author(s) -
Qian Liu,
Hongxia Fan,
Ying Ju,
Lizhao Chen,
Xin Li,
Xin Ye,
Yunjing Luo,
Changfei Li,
Songdong Meng
Publication year - 2019
Publication title -
journal of general virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.55
H-Index - 167
eISSN - 1465-2099
pISSN - 0022-1317
DOI - 10.1099/jgv.0.001289
Subject(s) - hbsag , virology , biology , hepatitis b virus , downregulation and upregulation , hepatitis b virus pre beta , viral replication , cccdna , transcription (linguistics) , hbeag , virus , hepatitis b virus dna polymerase , gene , biochemistry , linguistics , philosophy
In hepatitis B virus (HBV) infection, the virus produces redundant hepatitis B surface antigen (HBsAg) that plays a key role in driving T-cell tolerance and viral persistence. However, currently available anti-HBV agents have no direct effect on HBsAg transcription and protein expression. In this study, we designed a heat shock protein gp96 inhibitor p37 with the cell penetrating peptide PTD (protein transduction domain of trans-activator of transcription), which mediated p37 internalization into hepatocytes. PTD-p37 effectively suppressed HBsAg expression and viral replication both in vitro and in vivo. We further provide evidence that PTD-p37 suppressed HBV enhancer/promoter activity via p53 upregulation. Moreover, PTD-p37 had antiviral activity against a lamivudine-resistant HBV strain. Considering that suppression of HBsAg expression is a major goal for treatment of HBV infection, our results provide a basis for developing a new therapeutic approaches targeting host factors against viral expression.