Simvastatin exerts anti-hepatitis B virus activity by inhibiting expression of minichromosome maintenance protein 7 in HepG2.2.15 cells

  • Authors:
    • Wenjie Li
    • Fei Cao
    • Juan Li
    • Zhixin Wang
    • Yu Ren
    • Zheyong Liang
    • Peijun Liu
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  • Published online on: October 20, 2016     https://doi.org/10.3892/mmr.2016.5868
  • Pages: 5334-5342
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Abstract

Simvastatin (SIM), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been reported to inhibit the activity of hepatitis B virus (HBV), however, the mechanism underlying its antiviral function remains unknown. Minichromosome maintenance (MCM) 7, a component of the MCM complex, has been reported to act as an important host factor aiding virus genome replication in host cells. The present study demonstrated that downregulation of MCM7 inhibited the expression of proteins transferred by adenoviral vectors. This suggests an association between MCM7 and viral DNA expression. Thus, the current study aimed to investigate whether SIM affected MCM7 expression. Notably, the results of the present study indicated that following exposure to SIM the protein expression levels of MCM7 in HepG2.2.15, a human HBV‑transfected liver cell line, was decreased. In addition, the HBV DNA replication in the cell line was suppressed. As quantitative polymerase chain reaction experiments demonstrated that SIM did not downregulate the mRNA expression level of MCM7, the current study further investigated whether SIM affects the translation of MCM7. Western blot experiments indicated that SIM improved the activation of eukaryotic initiation factor‑2α (eIF2α), a protein synthesis initiation factor, and upregulated the upstream factors of eIF2α, protein kinase RNA‑like endoplasmic reticulum kinase, which is regulated by the liver kinase B1 (LKB1)‑AMP‑activated protein kinase (AMPK) signaling pathway. These results indicated that SIM induced HBV downregulation via an MCM‑dependent mechanism, and SIM may inhibit MCM7 expression by increasing the phosphorylation of eIF2α, which is mediated by the LKB1-AMPK signaling pathway.
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December-2016
Volume 14 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Li W, Cao F, Li J, Wang Z, Ren Y, Liang Z and Liu P: Simvastatin exerts anti-hepatitis B virus activity by inhibiting expression of minichromosome maintenance protein 7 in HepG2.2.15 cells. Mol Med Rep 14: 5334-5342, 2016
APA
Li, W., Cao, F., Li, J., Wang, Z., Ren, Y., Liang, Z., & Liu, P. (2016). Simvastatin exerts anti-hepatitis B virus activity by inhibiting expression of minichromosome maintenance protein 7 in HepG2.2.15 cells. Molecular Medicine Reports, 14, 5334-5342. https://doi.org/10.3892/mmr.2016.5868
MLA
Li, W., Cao, F., Li, J., Wang, Z., Ren, Y., Liang, Z., Liu, P."Simvastatin exerts anti-hepatitis B virus activity by inhibiting expression of minichromosome maintenance protein 7 in HepG2.2.15 cells". Molecular Medicine Reports 14.6 (2016): 5334-5342.
Chicago
Li, W., Cao, F., Li, J., Wang, Z., Ren, Y., Liang, Z., Liu, P."Simvastatin exerts anti-hepatitis B virus activity by inhibiting expression of minichromosome maintenance protein 7 in HepG2.2.15 cells". Molecular Medicine Reports 14, no. 6 (2016): 5334-5342. https://doi.org/10.3892/mmr.2016.5868