Das Dipanwita, Sarkar Neelakshi, Sengupta Isha, Pal Ananya, Saha Debraj, Bandopadhyay Manikankana, Das Chandrima, Narayan Jimmy, Singh Shivram Prasad, Chakravarty Runu
Dipanwita Das, Neelakshi Sarkar, Ananya Pal, Debraj Saha, Manikankana Bandopadhyay, Runu Chakravarty, ICMR Virus Unit, Kolkata, ID and BG Hospital Campus, Kolkata 700010, India.
World J Gastroenterol. 2016 Dec 21;22(47):10341-10352. doi: 10.3748/wjg.v22.i47.10341.
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.
Toll样受体在不同感染中发挥重要的抗病毒作用。本研究旨在探讨Toll样受体4(TLR4)在乙型肝炎病毒(HBV)感染中的作用。
在用TLR4特异性配体触发HepG2.2.15细胞后,使用实时PCR分析TLR4信号分子、细胞周期调节因子和HBV DNA病毒载量的转录情况。利用显微镜技术分析TLR4激活时核因子(NF)-κB的易位。分别使用蛋白质印迹法和流式细胞术进行蛋白质和细胞周期分析。
本研究表明,TLR4激活可抑制HBV感染。由于HBV受到抑制,宿主因子出现了一些变化,包括G1/S细胞周期阻滞的部分解除以及宿主表观遗传标记的变化。最后,观察到TLR4的抗病毒作用是通过NF-κB途径发生的。
该研究表明,HBV感染中TLR4的激活会导致肝细胞微环境发生变化,未来可用于开发有前景的治疗靶点。