Wieland Stefan F, Vega Raquel G, Müller Rolf, Evans Claire F, Hilbush Brian, Guidotti Luca G, Sutcliffe J Gregor, Schultz Peter G, Chisari Francis V
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
J Virol. 2003 Jan;77(2):1227-36. doi: 10.1128/jvi.77.2.1227-1236.2003.
We have previously shown that alpha/beta interferon (IFN-alpha/beta) and IFN-gamma inhibit hepatitis B virus (HBV) replication noncytopathically in the livers of HBV transgenic mice and in hepatocyte cell lines derived from these mice. The present study was designed to identify transcriptionally controlled hepatocellular genes that are tightly associated with the inhibition of HBV replication and that might, therefore, mediate the antiviral effect of these cytokines. Twenty-nine genes were identified, many of which have known or potential antiviral activity. Notably, multiple components of the immunoproteasome and ubiquitin-like proteins were strongly induced by both IFN-alpha/beta and IFN-gamma, as were a number of GTP-binding proteins, including GTPases with known antiviral activity, chemokines, signaling molecules, and miscellaneous genes associated with antigen processing, DNA-binding, or cochaperone activity and several expressed sequence tags. The results suggest that one or more members of this relatively small subset of genes may mediate the antiviral effect of IFN-alpha/beta and IFN-gamma against HBV. We have already exploited this information by demonstrating that the antiviral activity of IFN-alpha/beta and IFN-gamma is proteasome dependent.
我们之前已经表明，α/β干扰素（IFN-α/β）和IFN-γ在乙肝病毒（HBV）转基因小鼠肝脏以及源自这些小鼠的肝细胞系中，以非细胞病变的方式抑制HBV复制。本研究旨在鉴定与抑制HBV复制紧密相关且可能介导这些细胞因子抗病毒作用的转录调控肝细胞基因。共鉴定出29个基因，其中许多具有已知或潜在的抗病毒活性。值得注意的是，免疫蛋白酶体和类泛素蛋白的多个组分均被IFN-α/β和IFN-γ强烈诱导，一些GTP结合蛋白也是如此，包括具有已知抗病毒活性的GTP酶、趋化因子、信号分子，以及与抗原加工、DNA结合或共伴侣活性相关的其他基因和几个表达序列标签。结果表明，这一相对较小的基因子集的一个或多个成员可能介导IFN-α/β和IFN-γ对HBV的抗病毒作用。我们已经通过证明IFN-α/β和IFN-γ的抗病毒活性依赖蛋白酶体，利用了这一信息。
