Establishment and application of hepatitis B virus persistent replication model in IFNAR(-/-) mouse / 华中科技大学学报（医学）（英德文版）

The type I interferon and IFNAR play an important role in hepatitis B virus (HBV) infection and anti-HBV therapy. However, its mechanism of action is still poorly understood. To gain more insights into the role of type I interferon and type I interferon receptor (IFNAR) in HBV infection, we established an HBV persistent replication IFNAR knockout (IFNAR(-/-)) mouse model and preliminarily applied this model. At first, the progeny of IFNAR(-/-) mouse was reproduced. Then hydrodynamic injection with pAAV/HBV1.2 plasmid was conducted to establish the persistent HBV replication IFNAR(-/-) mouse model. At last, we applied this model to evaluate the effect of nucleoside analogues entecavir (ETV) on HBV replication. It was found that there was no difference in the serum HBsAg and HBeAg levels and HBcAg expression in the liver tissue between the ETV treated groups and normal saline (NS) treated group, but the serum HBV DNA levels were significantly suppressed 10, 25, 40 and 55 days after the ETV treatment [P=0.035, P=0.00, P=0.149 and P=0.084, IFNAR knockout (KO) control group vs. C57BL/6 ETV groups, respectively; P=0.081, P=0.001, P=0.243 and P=0.147, IFNAR KO control group vs. IFNAR KO ETV groups, respectively]. Interestingly, there was no difference in serum HBV DNA levels between the ETV treated IFNAR(-/-) and C57BL/6 mice. This result suggests that HBV suppression during ETV treatments doesn't depend on type I interferon and IFNAR. Collectively, persistent HBV replication IFNAR(-/-) mouse model that we established is a useful and convenient tool to detect the function of the type I interferon and IFNAR in HBV infection and anti-HBV treatments.

Expression of IFN-alpha/beta receptor in the PBMCs and liver of patients with hepatitis B and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of interferon (IFN)-alpha/beta receptor beta subunit (IFNAR2) in the patients' response to IFN-alpha therapy as influenced by the grade of chronic hepatic inflammation, and understand the relation of IFNAR2 expression in the peripheral blood mononuclear cells (PBMCs) with HBV infection.</p><p><b>METHODS</b>Liver tissue specimens were obtained from 21 patients with chronic hepatitis B for examination of the hepatic inflammation, and PBMCs were isolated from another 16 patients with chronic hepatitis B and 15 health control subjects. Both the hepatic tissues and PBMCs were examined for IFNAR2 expression using immunohistochemistry.</p><p><b>RESULTS</b>The 21 patients with chronic hepatitis B were divided into 3 groups according to the severity of hepatic inflammation, namely G(1) (n=3), G(2) (n=7) and G(3) (n=11) groups. The patients in G(3) group showed had significantly higher IFNAR2 expressions in liver (25.1307-/+7.0700) than those of the G(1) (5.6913-/+1.8422) and G(2) (7.4706-/+5.3572) groups (P=0.000). The IFNAR2 levels in the PBMCs, however, did not show significant difference between patients with chronic hepatitis B and the healthy control subjects.</p><p><b>CONCLUSION</b>In patients with chronic hepatitis B, IFNAR2 expression level is positively correlated to the severity of hepatic inflammation, and increased IFNAR2 expression in severe hepatic inflammation is therefore likely to result in increased response rate to INF-alpha therapy. The expression of IFNAR2 in the PBMCs is not associated with HBV infection.</p>