RNase L inhibitor is induced during human immunodeficiency virus type 1 infection and down regulates the 2-5A/RNase L pathway in human T cells
RNase L inhibitor is induced during human immunodeficiency virus type 1 infection and down regulates the 2-5A/RNase L pathway in human T cells
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DOI：
10.1128/jvi.73.1.290-296.1999
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发表时间：
1999-01-01
影响因子：
5.4
通讯作者：
Bisbal, C
中科院分区：
文献类型：
--
作者：
Martinand, C;Montavon, C;Bisbal, C
干扰素调节的2-5A/核糖核酸酶L通路在这些细胞因子的抗病毒和抗增殖活性中起主要作用，然而，一些病毒已经进化出逃避2-5A/核糖核酸酶L通路的抗病毒活性的策略。在此背景下，我们克隆了核糖核酸酶L抑制蛋白的编码基因，该蛋白特异性地抑制核糖核酸酶L，其在微小核糖核酸病毒感染细胞中的调节表达下调了2-5A/核糖核酸酶L通路的活性。我们在这里显示，在人类免疫缺陷病毒1型感染过程中，Rli增加，这可能与已被描述发生在HIV感染细胞中的核糖核酸酶L活性下调有关。为了建立这些观察结果之间可能的因果关系，我们用RLI正义或反义cDNA表达载体稳定地转染了H9细胞。Rli的过表达导致核糖核酸酶L活性下降和HIV产量加倍增加。艾滋病毒复制的增加与艾滋病毒RNA和蛋白质的增加相关。相反，在表达Rli反义基因的克隆中，Rli水平的降低逆转了与艾滋病毒增殖相关的核糖核酸酶L活性的抑制，并导致病毒载量减少了三倍。这种抗HIV活性与HIV RNA和蛋白质的减少有关。这些发现表明，Rli通过调节核糖核酸酶L的活性而严重损害HIV的复制，并提示Rli参与了对HIV感染过程中观察到的2-5A/RNaseL系统的抑制。
The interferon-regulated 2-5A/RNase L pathway plays a major role in the antiviral and antiproliferative activities of these cytokines, Several viruses, however, have evolved strategies to escape the antiviral activity of the 2-5A/RNase L pathway. In this context, we have cloned a cDNA coding for the RNase L inhibitor (RLI), a protein that specifically inhibits RNase L and whose regulated expression in picornavirus-infected cells down regulates the activity of the 2-5A/RNase L pathway. We show here that RLI increases during the course of human immunodeficiency virus type 1 (HIV-1) infection, which may be related to the downregulation of RNase L activity that has been described to occur in HIV-infected cells. In order to establish a possible causal relationship between these observations, we have stably transfected H9 cells with RLI sense or antisense cDNA-expressing vectors. The overexpression of RLI causes a decrease in RNase L activity and a twofold enhance ment of HIV production. This increase in HIV replication correlates with an increase in HIV RNA and proteins. In contrast, reduction of RLI levels in RLI antisense cDNA-expressing clones reverses the inhibition of RNase L activity associated with HIV multiplication and leads to a threefold decrease in the viral load. This anti-HIV activity correlated with a decrease in HIV RNA and proteins. These findings demonstrate that the level of RLI, via its modulation of RNase L activity, can severely impair HIV replication and suggest the involvement of RLI in the inhibition of the 2-5A/RNase L system observed during HIV infection.