Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection.

Yong Li,Shufeng Liu,Tiantian Zhu,Chuanlong Zhu,Jun Li,Fei Xiao,Faxi Wang

doi:10.1155/2016/3894816

Abstract

Interferon-α (IFN-α) has limited response rate in the treatment of chronic hepatitis B (CHB). The underlying mechanism of differential responsiveness to IFN remains elusive. It has been recently reported that SART1 mediates antiviral effects of IFN-α in the hepatitis C virus (HCV) cell culture model. In this study, we investigated the role of SART1 in antiviral activity of IFN-α against hepatitis B virus (HBV) using blood and liver biopsy samples from chronic hepatitis B patients treated with pegylated IFN-α and HepG2 cells transfected with cloned HBV DNA. We observed that the basal SART1 expression in liver and PBMCs before IFN treatment was significantly higher in responders than in nonresponders. Furthermore, baseline SART1 expression level positively correlated with the degree of HBV DNA and HBeAg decline after IFN treatment. Mechanistically, silencing SART1 abrogated the antiviral activity of IFN-α, reduced the expression of IFN-stimulated genes (ISGs) Mx, OAS, and PKR, and attenuated JAK-STAT signaling in HepG2 cells, suggesting that SART1 regulates IFN-mediated antiviral activity through JAK-STAT signaling and ISG expression. Our study elucidates the important role of SART1 in IFN-mediated anti-HBV response and provides new insights into understanding variation of IFN treatment response in CHB patients.

Highlights

Hepatitis B remains a global health problem with 350–400 million people being chronically infected with hepatitis B virus worldwide [1, 2]
Using immunehistochemical staining and qRT-PCR, we first analyzed the expression of SART1 in both live biopsy and PBMCs from chronic hepatitis B (CHB) patients before IFN-α treatment
Among all the CHB patients receiving IFN treatment, pretreatment SART1 expression in PBMCs was positively associated with hepatitis B virus (HBV) DNA and HBV e-Ag (HBeAg) decline from 0 to 12 weeks (Figure 1(c))

Summary

Introduction

Hepatitis B remains a global health problem with 350–400 million people being chronically infected with hepatitis B virus worldwide [1, 2]. These patients are prone to life threatening complications such as HBV acute-on-chronic liver failure (ACLF) [3], cirrhosis, and hepatocellular carcinoma (HCC) [4]. There are currently two classes of agents approved for the treatment of chronic hepatitis B (CHB): nucleos(t)ide analogues and standard or pegylated interferon-α (Peg-IFNα) [5]. Substantial progress has been made in treatment of hepatitis B in the past decade, less than 30% of the CHB patients show sustained response to IFN therapy

Methods

Results

Discussion

Conclusion