Analysis Of The Functional Region For Anti-IFN-α Effects By Terminal Protein Of HBV DNA Polymerase

Infection of the Hepatitis B virus (HBV) resulted in a broad spectrum of clinical manifestations, including asymptomatic carrier, acute hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma. Interferon-α(IFN-α) is one of the most commonly used drugs for the treatment of hepatitis B, it can inhibit and ultimately clear the HBV by immunomodulation and establishing intracellular antiviral state. However, it was found that approximately two thirds of IFN-αtreated patients showed IFN-αnon-responseness, i.e., no loss of HBeAg and reduction of serum HBV DNA lever. It was considered that the IFN-αnon-responseness of HBV was associated with HBV DNA polymerase. Foster et al demonstrated that terminal protein (TP) of HBV DNA polymerase could dramatically inhibit the cellular response to IFN-αby blocking the IFN pathway, yet the related functional region of TP was remained largely obscure. So the aim of this study is to analyze and determine the functional region of TP for anti-IFN-αeffects by constructing a series of deletants of TP gene. We hope that this study will not only be helpful for deep understanding of anti-IFN-αeffects by HBV, but also make for developing new anti-HBV therapeutic drugs.The first part of this study was aimed to set up a criterion to quantify the strength of the cellular responseness to IFN-α. To address this issue, the IFN-αresponse reporter vector p6-16CAT was constructed by insertion of the promoter region of human 6-16 gene (one kind of IFN-αinducible gene) into the upstream of CAT (Chloramphenicol acetyltransferase) gene. The results demonstrated that when Huh7 hepatocytes were transfected with p6-16CAT and treated with IFN-α, the cellular CAT was increased significantly, and showed the dose-effect relationship with the...