A peptide-based inhibitor of gp96 suppresses HBsAg expression and HBV replication by upregulation of p53. (17th June 2019)

• Record Type: Journal Article
• Authors: Qian, Liyuan; Fan, Hongxia; Ju, Ying; Chen, Lizhao; Li, Xin; Ye, Xin; Luo, Yunjing; Li, Changfei; Meng, Songdong
• Is Part Of: Journal of general virology. Volume 100:Number 8(2019)
• Page Start: 1241
• Page End: 1252
• Publication Date: 2019-06-17
• Subjects: HBV -- gp96 inhibitor -- p53 -- HBsAg; Virology -- Periodicals; Viruses; Microbiology; Virology; Virologie -- Périodiques; Microbiologie -- Périodiques; Virology; Virologie; Virologie; Electronic journals; Periodical; Periodicals; 579.2
• DOI: 10.1099/jgv.0.001289
• Languages: English
• ISSNs: 0022-1317

Abstract

Abstract : 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.