The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0.
The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0.
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DOI：
10.1371/journal.ppat.1002084
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发表时间：
2011-06
期刊：
影响因子：
6.7
通讯作者：
Weitzman MD
中科院分区：
文献类型：
--
作者：
Lilley CE;Chaurushiya MS;Boutell C;Everett RD;Weitzman MD
响应疱疹病毒感染的细胞限制因子包括 ND10 成分 PML、Sp100 和 hDaxx。在 HSV-1 感染的初始阶段，含有这些 ND10 蛋白的新型亚核结构与传入的病毒基因组相关。我们报告说，一些细胞 DNA 损伤反应蛋白也会重新定位到与传入病毒基因组相关的位点，在那里它们有助于细胞的前线防御。我们表明，DNA 修复蛋白向这些位点的募集独立于 ND10 成分，而是由细胞泛素连接酶 RNF8 和 RNF168 协调。病毒蛋白 ICP0 以 RNF8 和 RNF168 为目标进行降解，从而防止抑制性泛素标记的沉积并抵消这种修复蛋白的募集。这项研究强调了细胞 DNA 损伤识别和病毒基因组识别之间的重要相似之处，并将 RNF8 和 RNF168 添加到有助于对疱疹病毒感染进行内在抗病毒防御的因素列表中。细胞 DNA 损伤反应途径监测基因组 DNA 的损伤。我们研究了细胞 DNA 损伤反应蛋白是否也能对传入的病毒遗传物质做出反应以及它们如何影响病毒生长。使用 1 型单纯疱疹病毒 (HSV-1)，我们提供的证据表明 DNA 修复蛋白在感染后最早的时间被激活，并且它们在与传入病毒基因组相关的位点上物理积累。这些 DNA 修复蛋白的一部分会沉积抑制性泛素标记，招募其他 DNA 修复蛋白，并限制病毒基因组的转录。我们证明，病毒通过靶向关键 DNA 修复蛋白进行降解来克服这种抗病毒防御。我们的研究将这些 DNA 修复蛋白介质添加到针对 HSV-1 具有活性的内在抗病毒防御因子列表中，并证明细胞对外来 DNA 的识别的许多方面与对细胞损伤的识别和响应是平行的。
Cellular restriction factors responding to herpesvirus infection include the ND10 components PML, Sp100 and hDaxx. During the initial stages of HSV-1 infection, novel sub-nuclear structures containing these ND10 proteins form in association with incoming viral genomes. We report that several cellular DNA damage response proteins also relocate to sites associated with incoming viral genomes where they contribute to the cellular front line defense. We show that recruitment of DNA repair proteins to these sites is independent of ND10 components, and instead is coordinated by the cellular ubiquitin ligases RNF8 and RNF168. The viral protein ICP0 targets RNF8 and RNF168 for degradation, thereby preventing the deposition of repressive ubiquitin marks and counteracting this repair protein recruitment. This study highlights important parallels between recognition of cellular DNA damage and recognition of viral genomes, and adds RNF8 and RNF168 to the list of factors contributing to the intrinsic antiviral defense against herpesvirus infection. The cellular DNA damage response pathway monitors damage to genomic DNA. We investigated whether cellular DNA damage response proteins can also respond to incoming viral genetic material and how they impact virus growth. Using Herpes Simplex Virus type 1 (HSV-1), we present evidence that DNA repair proteins are activated at the earliest times post-infection, and that they physically accumulate at sites associated with incoming viral genomes. A subset of these DNA repair proteins deposit repressive ubiquitin marks, recruit other DNA repair proteins, and limit transcription from the viral genomes. We demonstrate that the virus overcomes this anti-viral defense by targeting key DNA repair proteins for degradation. Our study adds these DNA repair protein mediators to the list of intrinsic antiviral defense factors active against HSV-1, and demonstrates that many aspects of the cellular recognition of foreign DNA parallel the recognition and response to cellular damage.
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临时细胞性白血病核体的行为是DNA损伤传感器，其对DNA双链断裂的反应由NBS1和激酶ATM，CHK2和ATR调节。
DOI：
10.1083/jcb.200604009
发表时间：
2006-10-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dellaire G;Ching RW;Ahmed K;Jalali F;Tse KC;Bristow RG;Bazett-Jones DP
通讯作者：
Bazett-Jones DP
影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
8
作者：
Carbone, R;Pearson, M;Pelicci, PG
通讯作者：
Pelicci, PG
影响因子：
5.4
作者：
Everett, RD;Boutell, C;Orr, A
通讯作者：
Orr, A
影响因子：
64.8
作者：
通讯作者：
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