Anti-viral role of toll like receptor 4 in hepatitis B virus infection: An in vitro study

World J Gastroenterol. 2016 Dec 21;22(47):10341-10352. doi: 10.3748/wjg.v22.i47.10341.

Abstract

Aim: Toll like receptors plays a significant anti-viral role in different infections. The aim of this study was to look into the role of toll like receptor 4 (TLR4) in hepatitis B virus (HBV) infection.

Methods: Real time PCR was used to analyze the transcription of TLR4 signaling molecules, cell cycle regulators and HBV DNA viral load after triggering the HepG2.2.15 cells with TLR4 specific ligand. Nuclear factor (NF)-κB translocation on TLR4 activation was analyzed using microscopic techniques. Protein and cell cycle analysis was done using Western Blot and FACS respectively.

Results: The present study shows that TLR4 activation represses HBV infection. As a result of HBV suppression, there are several changes in host factors which include partial release in G1/S cell cycle arrest and changes in host epigenetic marks. Finally, it was observed that anti-viral action of TLR4 takes place through the NF-κB pathway.

Conclusion: The study shows that TLR4 activation in HBV infection brings about changes in hepatocyte microenvironment and can be used for developing a promising therapeutic target in future.

Keywords: Cell cycle; Epigenetic marks; Hepatitis B virus; Innate immune response; Toll like receptor 4.

MeSH terms

  • Active Transport, Cell Nucleus
  • Cellular Microenvironment
  • DNA Methylation
  • DNA, Viral / genetics
  • Dose-Response Relationship, Drug
  • Epigenesis, Genetic
  • G1 Phase Cell Cycle Checkpoints
  • Hep G2 Cells
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity*
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / metabolism*
  • Hepatitis B, Chronic / prevention & control
  • Hepatitis B, Chronic / virology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Hepatocytes / virology*
  • Host-Pathogen Interactions
  • Humans
  • Ligands
  • Lipopolysaccharides / pharmacology
  • NF-kappa B / metabolism
  • Signal Transduction
  • Time Factors
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*
  • Viral Load

Substances

  • DNA, Viral
  • Ligands
  • Lipopolysaccharides
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4