A peptide-based inhibitor of gp96 suppresses HBsAg expression and HBV replication by upregulation of p53
Qian, Liyuan and Fan, Hongxia and Ju, Ying and Chen, Lizhao and Li, Xin and Ye, Xin and Luo, Yunjing and Li, Changfei and Meng, Songdong,, 100, 1241-1252 (2019),
doi = https://doi.org/10.1099/jgv.0.001289,
publicationName = Microbiology Society,
issn = 0022-1317,
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.,
language=,
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