Citation: Xinna Ma, Heng Li, Ying Gong, Feifei Liu, Xiankun Tong, Fenghua Zhu, Xiaoqian Yang, Li Yang, Jianping Zuo. Psoralen inhibits hepatitis B viral replication by down-regulating the host transcriptional machinery of viral promoters .VIROLOGICA SINICA, 2022, 37(2) : 256-265.  http://dx.doi.org/10.1016/j.virs.2022.01.027

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

  • Corresponding author: Li Yang, yangli@simm.ac.cn
    Jianping Zuo, jpzuo@simm.ac.cn
  • Received Date: 30 May 2021
    Accepted Date: 18 October 2021
    Available online: 25 January 2022
  • 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 HepG2.2.15 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 pre-core/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 PGC1α to the HBV promoter. Overall, our results demonstrate that psoralen suppresses HBV RNA transcription by down-regulating the expression of FOXO1 resulting in a reduction of HBV replication.

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

      Corresponding author: Li Yang, yangli@simm.ac.cn
      Corresponding author: Jianping Zuo, jpzuo@simm.ac.cn
    • a Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Abstract: 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 HepG2.2.15 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 pre-core/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 PGC1α to the HBV promoter. Overall, our results demonstrate that psoralen suppresses HBV RNA transcription by down-regulating the expression of FOXO1 resulting in a reduction of HBV replication.

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