The C4 protein encoded by tomato leaf curl Yunnan virus reverses transcriptional gene silencing by interacting with NbDRM2 and impairing its DNA-binding ability.
The C4 protein encoded by tomato leaf curl Yunnan virus reverses transcriptional gene silencing by interacting with NbDRM2 and impairing its DNA-binding ability.
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番茄曲叶云南病毒编码的C4蛋白通过与NbDRM2相互作用并干扰其DNA结合能力来逆转转录基因沉默
DOI：
10.1371/journal.ppat.1008829
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发表时间：
2020-10
期刊：
影响因子：
6.7
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Mei Y;Wang Y;Li F;Zhou X
在植物中，胞嘧啶 DNA 甲基化是针对双生病毒的有效防御机制，因为病毒基因组的甲基化会导致转录基因沉默 (TGS)。作为一种反防御机制，双生病毒编码病毒蛋白来抑制病毒 DNA 甲基化和 TGS。然而，病毒蛋白抑制 TGS 的分子机制仍不完全清楚。在这项研究中，我们发现云南番茄曲叶病毒（TLCYnV）编码的C4蛋白通过与NbDRM2（甲基循环中关键的DNA甲基转移酶）相互作用并损害其DNA结合能力来抑制病毒基因组的甲基化。我们发现 NbDRM2 催化病毒基因组特定胞嘧啶位点上甲基的添加，因此在抗病毒防御中发挥重要作用。强调了 C4 介导的 NbDRM2 活性抑制的相关性，与野生型 TLCYnV 感染的植物相比，被 TLCYnV 感染的植物产生 C4（S43A）（一种不能与 NbDRM2 相互作用的 C4 点突变版本），表现出更温和的症状和更低的病毒积累，同时病毒 DNA 甲基化增强。在 16c-TGS 本塞姆氏烟草植物中，TLCYnV C4 的表达而非 NbDRM2 相互作用受损的 C4(S43A) 突变体的表达导致 GFP 的恢复，而 GFP 是 TGS 抑制的代表。这项研究为双生病毒抑制 TGS 的分子机制提供了新的见解，并揭示了一种基于甲基转移酶 NbDRM2 失活的新病毒策略。干扰转录基因沉默 (TGS) 对于 DNA 病毒在植物细胞中感染和复制至关重要。双生病毒科的一些成员编码能够抑制 TGS 的 C4 蛋白，从而增强毒力。然而，C4 介导的 TGS 抑制的分子机制仍不完全清楚。这项研究表明，番茄曲叶云南病毒编码的C4蛋白与NbDRM2（甲基循环中的关键DNA甲基转移酶）相互作用，并干扰其结合病毒DNA的能力。结果，病毒基因组的甲基化受损，从而有利于病毒复制和传播。我们的研究结果揭示了双生病毒对抗抗病毒 DNA 甲基化的新策略，从而为病毒和宿主之间的军备竞赛提供了新的线索。
In plants, cytosine DNA methylation is an efficient defense mechanism against geminiviruses, since methylation of the viral genome results in transcriptional gene silencing (TGS). As a counter-defense mechanism, geminiviruses encode viral proteins to suppress viral DNA methylation and TGS. However, the molecular mechanisms by which viral proteins contribute to TGS suppression remain incompletely understood. In this study, we found that the C4 protein encoded by tomato leaf curl Yunnan virus (TLCYnV) suppresses methylation of the viral genome through interacting with and impairing the DNA-binding ability of NbDRM2, a pivotal DNA methyltransferase in the methyl cycle. We show that NbDRM2 catalyzes the addition of methyl groups on specific cytosine sites of the viral genome, hence playing an important role in anti-viral defense. Underscoring the relevance of the C4-mediated suppression of NbDRM2 activity, plants infected by TLCYnV producing C4(S43A), a point mutant version of C4 unable to interact with NbDRM2, display milder symptoms and lower virus accumulation, concomitant with enhanced viral DNA methylation, than plants infected by wild-type TLCYnV. Expression of TLCYnV C4, but not of the NbDRM2-interaction compromised C4(S43A) mutant, in 16c-TGS Nicotiana benthamiana plants results in the recovery of GFP, a proxy for suppression of TGS. This study provides new insights into the molecular mechanisms by which geminiviruses suppress TGS, and uncovers a new viral strategy based on the inactivation of the methyltransferase NbDRM2. Interfering with transcriptional gene silencing (TGS) is essential for DNA viruses to infect and replicate in plant cells. Some members of the Geminiviridae family encode a C4 protein capable of inhibiting TGS, hence promoting virulence. However, the molecular mechanism underlying the C4-mediated TGS suppression is still incompletely understood. This study demonstrates that the C4 protein encoded by tomato leaf curl Yunnan virus interacts with NbDRM2, a pivotal DNA methyltransferase in the methyl cycle, and interferes with its ability to bind the viral DNA. As a result, methylation of the viral genome is impaired, which in turn favours viral replication and spread. Our results uncover a novel strategy deployed by geminiviruses to counter anti-viral DNA methylation, hence shedding new light onto the arms race between viruses and hosts.
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影响因子：
5.4
作者：
Cui, XF;Tao, XR;Zhou, XP
通讯作者：
Zhou, XP
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2.6
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作者：
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14.8
作者：
Kaufmann, Kerstin;Muino, Jose M.;Angenent, Gerco C.
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