Published online Dec 21, 2016. doi: 10.3748/wjg.v22.i47.10341
Peer-review started: June 27, 2016
First decision: August 29, 2016
Revised: October 1, 2016
Accepted: November 16, 2016
Article in press: November 16, 2016
Published online: December 21, 2016
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.
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.
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.
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.
Core tip: The study delves into the role of toll like receptor 4 (TLR4) in hepatitis B virus (HBV) infection. Inciting TLR4 brings about drastic changes in viral and host responses in hepatocyte niche. Stimulating TLR4 represses viral replication and alters important host gene expression. Virus induced G1/S cell cycle arrest is partially released on viral elimination which is corroborated with the expression of chief cell cycle regulators. Further, we have observed activation of epigenetic signatures H3K9Ac/H3K18Ac, on viral suppression post TLR4 activation. Thus, this work is important in perspective of the role of TLR4 during HBV infection in hepatocyte microenvironment.