Six RNA viruses and forty-one hosts: viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems.
Six RNA viruses and forty-one hosts: viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems.
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DOI：
10.1371/journal.ppat.1000764
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发表时间：
2010-02-12
期刊：
影响因子：
6.7
通讯作者：
Fire AZ
中科院分区：
文献类型：
--
作者：
Parameswaran P;Sklan E;Wilkins C;Burgon T;Samuel MA;Lu R;Ansel KM;Heissmeyer V;Einav S;Jackson W;Doukas T;Paranjape S;Polacek C;dos Santos FB;Jalili R;Babrzadeh F;Gharizadeh B;Grimm D;Kay M;Koike S;Sarnow P;Ronaghi M;Ding SW;Harris E;Chow M;Diamond MS;Kirkegaard K;Glenn JS;Fire AZ
我们使用多路复用高通量测序来表征动物细胞病毒感染期间发生的小RNA群体的变化。基于小RNA的机制，如RNA干扰（RNAi）已经在植物和无脊椎动物系统中被证明在宿主对病毒感染的反应中发挥关键作用。尽管在哺乳动物细胞中存在关键RNAi效应通路的同系物，并且可以启动RNAi介导的实验靶mrna降解，但这些反应在哺乳动物宿主-病毒相互作用中的作用仍有待研究。在41个实验易感和耐药宿主系统中检测了6种不同的病毒。我们从所有六种病毒中鉴定出病毒衍生的小RNA (vsRNAs)，其总丰度从“极少”（小于细胞小RNA的0.1%）到高度丰富（与丰富的微RNA“miRNAs”相当）不等。除了在感染期间出现vsrna外，我们还看到宿主miRNA谱的一些特定变化。对于一些更详细的感染模型，RNAi和干扰素途径调节了vsrna的丰度。我们还发现了vsRNAs群体存在的证据，这些vsRNAs以零到三个核苷酸3 '悬垂的双工sirna的形式存在。使用携带丙型肝炎复制子的细胞群，我们观察到sirna链选择性加载到Argonaute复合物上。这些实验将vsrna定义为动物病毒与其宿主之间相互作用的一个可能组成部分。来自具有RNA基因组的入侵病毒的短RNA是植物、蠕虫和苍蝇抗病毒免疫的重要组成部分。这些短rna的调控产生，以及它们与免疫装置的结合，对于抑制这些生物体中的病毒生长至关重要。哺乳动物有必要的蛋白质成分来产生这些病毒衍生的短RNA（“vsRNAs”），这就提出了一个问题，即哺乳动物中的vsRNAs是否是RNA病毒感染的一般特征。我们对丙型肝炎、脊髓灰质炎、登革热、水疱性口炎和西尼罗河病毒在广泛宿主库中的研究表明，RNA病毒衍生的vsRNA产生的普遍性，以及细胞短RNA装置在哺乳动物细胞中参与这些vsRNA的能力。对vsRNA和宿主衍生的短RNA群体的详细分析表明，病毒感染和短RNA群体之间相互作用的共同特征和病毒特异性特征。在这项工作中描述的vsRNA群体代表了病毒发病机制和宿主反应的一个新维度。
We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection in animal cells. Small RNA-based mechanisms such as RNA interference (RNAi) have been shown in plant and invertebrate systems to play a key role in host responses to viral infection. Although homologs of the key RNAi effector pathways are present in mammalian cells, and can launch an RNAi-mediated degradation of experimentally targeted mRNAs, any role for such responses in mammalian host-virus interactions remains to be characterized. Six different viruses were examined in 41 experimentally susceptible and resistant host systems. We identified virus-derived small RNAs (vsRNAs) from all six viruses, with total abundance varying from “vanishingly rare” (less than 0.1% of cellular small RNA) to highly abundant (comparable to abundant micro-RNAs “miRNAs”). In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host miRNA profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We also found evidence for populations of vsRNAs that exist as duplexed siRNAs with zero to three nucleotide 3′ overhangs. Using populations of cells carrying a Hepatitis C replicon, we observed strand-selective loading of siRNAs onto Argonaute complexes. These experiments define vsRNAs as one possible component of the interplay between animal viruses and their hosts. Short RNAs derived from invading viruses with RNA genomes are important components of antiviral immunity in plants, worms and flies. The regulated generation of these short RNAs, and their engagement by the immune apparatus, is essential for inhibiting viral growth in these organisms. Mammals have the necessary protein components to generate these viral-derived short RNAs (“vsRNAs”), raising the question of whether vsRNAs in mammals are a general feature of infections with RNA viruses. Our work with Hepatitis C, Polio, Dengue, Vesicular Stomatitis, and West Nile viruses in a broad host repertoire demonstrates the generality of RNA virus-derived vsRNA production, and the ability of the cellular short RNA apparatus to engage these vsRNAs in mammalian cells. Detailed analyses of vsRNA and host-derived short RNA populations demonstrate both common and virus-specific features of the interplay between viral infection and short RNA populations. The vsRNA populations described in this work represent a novel dimension in both viral pathogenesis and host response.
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影响因子：
11.4
作者：
Elbashir, SM;Martinez, J;Tuschl, T
通讯作者：
Tuschl, T
DOI：
10.1073/pnas.89.11.4825
发表时间：
1992-06-01
影响因子：
11.1
作者：
CHANG, HW;WATSON, JC;JACOBS, BL
通讯作者：
JACOBS, BL
DOI：
10.1016/j.biocel.2008.04.015
发表时间：
2008-01-01
影响因子：
4
作者：
de Vries, Walter;Berkhout, Ben
通讯作者：
Berkhout, Ben
影响因子：
64.5
作者：
Gan, JH;Tropea, JE;Ji, XH
通讯作者：
Ji, XH
影响因子：
7.6
作者：
Crance, JM;Scaramozzino, N;Garin, D
通讯作者：
Garin, D