Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing

Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing
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DOI:
10.1016/j.immuni.2005.03.010
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发表时间:
2005-05-01
期刊:
影响因子:
32.4
通讯作者:
Jeang, KT
Jeang, KT
中科院分区:
医学1区
文献类型:
--
作者:
Bennasser, Y;Le, SY;Jeang, KT

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在植物和无脊椎动物中,RNA沉默是一种基于核酸的适应性免疫形式。相比之下,有颌脊椎动物进化出了复杂的基于蛋白质的适应性免疫。尽管短干扰RNA(siRNA)已被用作人工工具来沉默人类细胞中的病毒感染,但哺乳动物病毒是否会在脊椎动物细胞中自然引发这种免疫仍不清楚。在此,我们报道了以下证据:HIV - 1在其基因组中编码病毒siRNA前体,并且自然的HIV - 1感染会在人类细胞中引发基于核酸的免疫。为了对抗这种细胞防御,HIV - 1在其Tat蛋白中进化出了一种RNA沉默抑制因子(SRS)功能。Tat通过破坏Dicer将前体双链RNA加工成siRNA的能力,从而消除细胞的RNA沉默防御。
In plants and invertebrate animals, RNA silencing is a form of nucleic acid-based adaptive immunity. By contrast, jawed vertebrates have evolved complex protein-based adaptive immunity. Although short interfering RNAs (siRNAs) have been used as artificial tools to silence viral infection in human cells, it remains unknown whether mammalian viruses naturally elicit such immunity in vertebral cells. Here, we report the evidence that HIV-1 encodes viral siRNA precursors in its genome and that natural HIV-1 infection provokes nucleic acid-based immunity in human cells. To combat this cellular defense, HIV-1 has evolved in its Tat protein a suppressor of RNA silencing (SRS) function. Tat abrogates the cell's RNA-silencing defense by subverting the ability of Dicer to process precursor double-stranded RNAs into siRNAs.