Viral genome methylation as an epigenetic defense against geminiviruses
Viral genome methylation as an epigenetic defense against geminiviruses
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DOI：
10.1128/jvi.00719-08
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发表时间：
2008-09-01
影响因子：
5.4
通讯作者：
Bisaro, David M.
中科院分区：
文献类型：
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作者：
Raja, Priya;Sanville, Bradley C.;Bisaro, David M.
双生病毒通过双链DNA中间体使在植物细胞核中复制的单链DNA基因组发生侧链化，所述双链DNA中间体与细胞组蛋白结合以形成微型染色体。与大多数植物病毒一样，双生病毒被RNA沉默靶向，并编码抑制蛋白如AL 2和L2来对抗这种防御。这些相关蛋白质可以通过多种机制抑制沉默，其中之一涉及与腺苷激酶（ADK）相互作用并抑制腺苷激酶（ADK），腺苷激酶是与甲基循环相关的细胞酶，其产生S-腺苷甲硫氨酸，S-腺苷甲硫氨酸是一种必需的甲基转移酶辅因子。因此，我们假设病毒基因组是由小RNA定向甲基化靶向的。在这里，我们表明，拟南芥植物与突变的基因编码胞嘧啶或组蛋白H3赖氨酸9（H3 K9）甲基转移酶，RNA定向甲基化途径的组件，或ADK是双生病毒感染过敏。我们还表明，病毒DNA和相关的组蛋白H3在受感染的植物甲基化，胞嘧啶甲基化水平显着降低从甲基化缺陷突变体分离的病毒DNA。最后，我们证明了甜菜曲顶病毒L2（-）突变体DNA存在于从感染中恢复的组织中是高甲基化的，宿主恢复需要AGO 4，RNA指导的甲基化途径的一个组成部分。我们认为植物利用染色质甲基化作为防御DNA病毒，双生病毒通过抑制全局甲基化来对抗DNA病毒。此外，我们的研究结果表明，双生病毒可以成为植物基因组甲基化的有用模型，并表明有冗余的途径导致胞嘧啶甲基化。
Geminiviruses encapsidate single-stranded DNA genomes that replicate in plant cell nuclei through double-stranded DNA intermediates that associate with cellular histone proteins to form minichromosomes. Like most plant viruses, geminiviruses are targeted by RNA silencing and encode suppressor proteins such as AL2 and L2 to counter this defense. These related proteins can suppress silencing by multiple mechanisms, one of which involves interacting with and inhibiting adenosine kinase (ADK), a cellular enzyme associated with the methyl cycle that generates S-adenosyl-methionine, an essential methyltransferase cofactor. Thus, we hypothesized that the viral genome is targeted by small-RNA-directed methylation. Here, we show that Arabidopsis plants with mutations in genes encoding cytosine or histone H3 lysine 9 (H3K9) methyltransferases, RNA-directed methylation pathway components, or ADK are hypersensitive to geminivirus infection. We also demonstrate that viral DNA and associated histone H3 are methylated in infected plants and that cytosine methylation levels are significantly reduced in viral DNA isolated from methylation-deficient mutants. Finally, we demonstrate that Beet curly top virus L2(-) mutant DNA present in tissues that have recovered from infection is hypermethylated and that host recovery requires AGO4, a component of the RNA-directed methylation pathway. We propose that plants use chromatin methylation as a defense against DNA viruses, which geminiviruses counter by inhibiting global methylation. In addition, our results establish that geminiviruses can be useful models for genome methylation in plants and suggest that there are redundant pathways leading to cytosine methylation.