Psoralen inhibits hepatitis B viral replication by down-regulating the host transcriptional machinery of viral promoters  

作　　者：Xinna Ma Heng Li Ying Gong Feifei Liu Xiankun Tong Fenghua Zhu Xiaoqian Yang Li Yang Jianping Zuo 

机构地区：[1]Laboratory of Immunology and Virology,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [2]Laboratory of Immunopharmacology,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [3]University of Chinese Academy of Sciences,Beijing,100049,China

出　　处：《Virologica Sinica》2022年第2期256-265,共10页中国病毒学（英文版）

基　　金：supported by the National Science Fund (82104240);Shanghai Science and Technology Innovation Project (20S11906200);self-deployed scientific research projects (State Key Laboratory of Drug Research) (SIMM1903ZZ-03)。

摘　　要：The hepatitis B virus(HBV) is a global public health challenge due to its highly contagious nature. It is estimated that almost 300 million people live with chronic HBV infection annually. Although nucleoside analogs markedly reduce the risk of liver disease progression, the analogs do not fully eradicate the virus. As such, new treatment options and drugs are urgently needed. Psoralen is a nourishing monomer of Chinese herb and is known to inhibit virus replication and inactivate viruses. In this study, we evaluated the potential of psoralen as an anti-HBV agent.Quantitative PCR and Southern blot analysis revealed that psoralen inhibited HBV replication in Hep G2.2.15 cells in a concentration-dependent manner. Moreover, psoralen was also active against the 3TC/ETV-dual-resistant HBV mutant. Further investigations revealed that psoralen suppressed both HBV RNA transcription and core protein expression. The transcription factor FOXO1, a known target for PGC1α co-activation, binds to HBV precore/core promoter enhancer II region and activates HBV RNA transcription. Co-immunoprecipitation showed that psoralen suppressed the expression of FOXO1, thereby decreasing the binding of FOXO1 co-activator PGC1αto the HBV promoter. Overall, our results demonstrate that psoralen suppresses HBV RNA transcription by downregulating the expression of FOXO1 resulting in a reduction of HBV replication.

关 键 词：PSORALEN Hepatitis B virus(HBV) Forkhead box-O1(FOXO1) PPARγco-activator 1α(PGC1α) Transcription 

分 类 号：R373.21[医药卫生—病原生物学]