Lambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities.
Lambda and alpha interferons inhibit hepatitis B virus replication through a common molecular mechanism but with different in vivo activities.
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DOI：
10.1016/j.virol.2010.02.022
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发表时间：
2010-06-05
期刊：
影响因子：
3.7
通讯作者：
Robek MD
中科院分区：
文献类型：
--
作者：
Pagliaccetti NE;Chu EN;Bolen CR;Kleinstein SH;Robek MD
III型干扰素（IFN-λ1、2、3）诱导类似于IFN-α/β的抗病毒应答，但通过独特的受体介导其活性。我们发现，与IFN-α/β一样，IFN-λ阻止HBV衣壳的组装，表明两种信号通路通过单一抗病毒机制的会聚。与IFN-λ相反，结构相关的细胞因子白细胞介素（IL）-22仅最低限度地减少HBV复制。由IL-22激活的转录程序与IFN-λ诱导的转录程序几乎没有相似性，而是类似于由IL-6引发的应答。我们还发现鼠IFN-λ2在转基因小鼠肝脏中仅具有弱的抗HBV活性，而人IFN-λ2在血清中的活性与细胞因子对蛋白酶的敏感性相关。这些结果表明IFN-α/β和IFN-λ抗HBV应答通过单一分子机制起作用，并支持IFN-λ在抗病毒免疫中发挥局部而非全身作用的观点。
The type III interferons (IFN-λ1, 2, 3) induce an antiviral response similar to IFN-α/β, but mediate their activity through a unique receptor. We found that like IFN-α/β, IFN-λ prevents the assembly of HBV capsids, demonstrating convergence of the two signaling pathways through a single antiviral mechanism. In contrast to IFN-λ, the structurally related cytokine interleukin (IL)-22 only minimally reduced HBV replication. The transcriptional program activated by IL-22 displayed little similarity to that induced by IFN-λ, but instead resembled the response elicited by IL-6. We also found that murine IFN-λ2 had only weak antiviral activity against HBV in the liver of transgenic mice, and that human IFN-λ2 activity in serum correlated with the sensitivity of the cytokine to proteases. These results demonstrate that the IFN-α/β and IFN-λ anti-HBV responses operate through a single molecular mechanism, and support the notion that IFN-λ plays a local, rather than systemic, role in antiviral immunity.
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