标题: [英语,研究]Hepatitis B Virus Limits Response of Human Hepatocytes to Inter [打印本页] 作者: StephenW 时间: 2011-4-15 21:09 标题: [英语,研究]Hepatitis B Virus Limits Response of Human Hepatocytes to Inter
BACKGROUND & AIMS: Interferon (IFN)-α therapy is not effective for most patients with chronic hepatitis B virus (HBV) infection, for unclear reasons. We investigated whether HBV infection reduced IFN-α-mediated induction of antiviral defence mechanisms in human hepatocytes. METHODS: Human hepatocytes were injected into severe combined immune deficient mice (SCID/beige) that expressed transgenic urokinase plasminogen activator under control of the albumin promoter. Some mice were infected with HBV; infected and uninfected mice were given injections of human IFN-α. Changes in viral DNA and expression of human interferon-stimulated genes (ISGs) were measured by real-time PCR, using human-specific primers, and by immunohistochemistry. RESULTS: Median HBV viremia (0.8log) and intrahepatic loads of HBV RNA decreased 3-fold by 8 or 12 h after each injection of IFN-α, but then increased within 24 h. IFN-α activated expression of human ISGs and nuclear translocation of STAT-1 in human hepatocytes that repopulated the livers of uninfected mice. Although baseline levels of human ISGs were slightly increased in HBV-infected mice, compared with uninfected mice, IFN-α failed to increase expression of the ISGs OAS-1, MxA, MyD88, and TAP-1 (which regulates antigen presentation) in HBV-infected mice. Remarkably, IFN-α did not induce nuclear translocation of STAT-1 in HBV-infected human hepatocytes. Administration of the nucleoside analogue entecavir (for 20 days) suppressed HBV replication but did not restore responsiveness to IFN-α. CONCLUSIONS: HBV prevents induction of IFN-α signaling by inhibiting nuclear translocation of STAT-1; this can interfere with transcription of ISGs in human hepatocytes. These effects of HBV might contribute to the limited effectiveness of endogenous and therapeutic IFN-α in patients and promote viral persistence. 作者: StephenW 时间: 2011-4-15 21:11
胃肠病学杂志(2011年)0:。
乙型肝炎病毒的大小人肝细胞干扰素-α嵌合小鼠。
M ütgehetmann,T Bornscheuer,T福尔茨,午Allweiss,Jh的Bockmann,JM波洛克,胡洛斯,强彼得森,男Dandri