Activation of the interferon-inducible (2′-5′) oligoadenylate synthetase by the Epstein-Barr virus RNA, EBER-1
Activation of the interferon-inducible (2′-5′) oligoadenylate synthetase by the Epstein-Barr virus RNA, EBER-1
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DOI：
10.1006/viro.1999.9689
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发表时间：
1999-05-10
期刊：
影响因子：
3.7
通讯作者：
Clemens, MJ
中科院分区：
文献类型：
--
作者：
Sharp, TV;Raine, DA;Clemens, MJ
2 '-5'寡腺苷酸合成酶和蛋白激酶PKR都是干扰素诱导的双链RNA依赖性蛋白，在干扰素的抗病毒作用和细胞生长控制中发挥重要作用。这两种酶都被天然或合成的dsRNA以及具有广泛二级结构的单链RNA激活。本报告描述了EB病毒编码的小RNA EBER-1对2-5（A）合成酶活性的调节作用。我们证明EBER-1 RNA以剂量依赖性方式结合并激活人40-kDa 2-5（A）合成酶。EBER-1作为2-5（A）合成酶的激活剂的效率约为合成的双链RNA poly（I）/poly（C）的25%，并且poly（I）/poly（C）甚至在高浓度EBER-1的存在下进一步刺激酶活性。相反，EBER-1既不刺激也不抑制已被高浓度poly（I）/poly（C）激活的2-5（A）合成酶。竞争性结合测定表明，该酶对poly（I）/poly（C）的相对亲和力显著高于对EBER-1的相对亲和力。我们的数据表明，EBER-1与腺病毒的VAI RNA、HIV-1的TAR RNA和HTLV-1的Rex-RE RNA一样，能够激活2-5（A）合成酶。的.讨论了为什么几种病毒可以激活2-5（A）合成酶/RNase L-介导的RNA降解途径的重要性，（C）1999 Academic Press。
The 2'-5' oligoadenylate synthetases and the protein kinase PKR are both interferon-induced, double-stranded RNA-dependent proteins that play important roles in the antiviral effects of the interferons and in cellular growth control. Both enzymes are activated by natural or synthetic dsRNAs and by single-stranded RNAs that possess extensive secondary structure. This report describes the effects of the small Epstein-Barr virus-encoded RNA EBER-1 on the regulation of 2-5(A) synthetase activity. We demonstrate that EBER-1 RNA binds to and activates the human 40-kDa 2-5(A) synthetase in a dose-dependent manner. The efficiency of EBER-1 as an activator of 2-5(A) synthetase is approximately 25% of that of the synthetic double-stranded RNA poly(l)/poly(C), and poly(l)/poly(C) further stimulates enzyme activity even in the presence of a high concentration of EBER-1. Conversely EBER-1 neither stimulates nor inhibits 2-5(A) synthetase that has been activated by a high concentration of poly(l)/poly(C). Competitive binding assays suggest that the relative affinity of the enzyme for poly(l)/poly(C) is considerably higher than that for EBER-1. Our data indicate that EBER-1, like VAI RNA of adenovirus, TAR RNA of HIV-1, and Rex-RE RNA of HTLV-I, is able to activate the 2-5(A) synthetases. The. significance of why several viruses may activate the 2-5(A) synthetase/RNase L-mediated RNA degradation pathway is discussed, (C) 1999 Academic Press.