The recently identified Luman/CREB3-binding partner LRF (Luman/CREB3 recruitment factor) was shown to localize to discrete sub-nuclear foci. Luman is implicated in herpes simplex virus-1 (HSV-1) latency/reactivation and the unfolded protein response (UPR) pathway; therefore, we sought to characterize the formation of the LRF nuclear foci in the context of cellular signaling and HSV-1 replication. Here, we mapped the nuclear foci-targeting sequence to the central region containing the first leucine zipper (a.a.415-519), and found that the integrity of the whole region appears essential for LRF foci formation. LRF foci integrity was unaffected by inhibition of cellular DNA replication and translation, however, disruption of transcription resulted in altered LRF localization. When compared to other cellular and viral foci LRF co-localized with the nuclear receptor co-activator GRIP1, while the HSV-1 gene products ICP4, ICP27 and VP13/14 disrupted foci formation to varying degrees. Interestingly, cells over-expressing LRF were resistant to productive HSV-1 infection and this resistance was dependent upon protein targeting and an N-terminal transactivation domain. When LRF knockdown cells were subjected to primary infection, HSV-1 gene expression and progeny virus yield were enhanced by ∼3 fold compared to wildtype cells. Taken together, these results indicate that LRF is a key regulator that may act direct or indirectly as a repressor of essential genes required for productive viral infection.

中文翻译：

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Luman / CREB3募集因子（LRF / CREBRF）靶向核灶的特征及其在抑制单纯疱疹病毒1复制中的潜在作用。

最近鉴定出的Luman / CREB3结合伴侣LRF（Luman / CREB3募集因子）被定位于离散的亚核灶。Luman与单纯疱疹病毒1（HSV-1）潜伏期/重新激活和未折叠的蛋白应答（UPR）途径有关；因此，我们试图在细胞信号传导和HSV-1复制的背景下表征LRF核灶的形成。在这里，我们将靶向核病灶的序列映射到包含第一个亮氨酸拉链的中央区域（aa415-519），发现整个区域的完整性对于LRF病灶的形成显得至关重要。LRF灶的完整性不受细胞DNA复制和翻译抑制的影响，但是，转录的破坏导致LRF定位的改变。与其他细胞和病毒病灶相比，LRF与核受体共激活因子GRIP1共定位，而HSV-1基因产物ICP4，ICP27和VP13 / 14在不同程度上破坏了病灶形成。有趣的是，过表达LRF的细胞对生产性HSV-1感染具有抗性，而这种抗性取决于蛋白质靶向和N末端反式激活结构域。当LRF抑制的细胞受到初次感染时，与野生型细胞相比，HSV-1基因的表达和子代病毒的产量提高了约3倍。综上所述，这些结果表明，LRF是关键调节剂，可以直接或间接充当生产性病毒感染所需的必需基因的阻遏物。ICP27和VP13 / 14在不同程度上破坏了灶的形成。有趣的是，过表达LRF的细胞对生产性HSV-1感染具有抗性，而这种抗性取决于蛋白质靶向和N末端反式激活结构域。当LRF抑制的细胞受到初次感染时，与野生型细胞相比，HSV-1基因的表达和子代病毒的产量提高了约3倍。综上所述，这些结果表明LRF是关键调节剂，可以直接或间接充当生产性病毒感染所需必需基因的阻遏物。ICP27和VP13 / 14在不同程度上破坏了灶的形成。有趣的是，过表达LRF的细胞对生产性HSV-1感染具有抗性，而这种抗性取决于蛋白质靶向和N末端反式激活结构域。当LRF抑制的细胞受到初次感染时，与野生型细胞相比，HSV-1基因的表达和子代病毒的产量提高了约3倍。综上所述，这些结果表明，LRF是关键调节剂，可以直接或间接充当生产性病毒感染所需的必需基因的阻遏物。与野生型细胞相比，HSV-1基因表达和子代病毒产量提高了约3倍。综上所述，这些结果表明，LRF是关键调节剂，可以直接或间接充当生产性病毒感染所需的必需基因的阻遏物。与野生型细胞相比，HSV-1基因表达和子代病毒产量提高了约3倍。综上所述，这些结果表明，LRF是关键调节剂，可以直接或间接充当生产性病毒感染所需的必需基因的阻遏物。