Processivity factor of KSHV contains a nuclear localization signal and binding domains for transporting viral DNA polymerase into the nucleus
Processivity factor of KSHV contains a nuclear localization signal and binding domains for transporting viral DNA polymerase into the nucleus
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DOI：
10.1016/j.virol.2005.06.017
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发表时间：
2005-09-30
期刊：
影响因子：
3.7
通讯作者：
Ricciardi, RP
中科院分区：
文献类型：
--
作者：
Chen, YL;Ciustea, M;Ricciardi, RP
卡波西肉瘤相关的人疱疹病毒（KSHV）编码一种持续合成因子（PF-8，ORF 59），可形成同源二聚体并与病毒DNA聚合酶（Pol-8，ORF 9）结合。PF-8对于稳定模板DNA上的Pol-8是必不可少的，使得Pol-8可以连续地掺入核苷酸。在这里，这两种病毒蛋白质的细胞内相互作用，通过共聚焦免疫荧光显微镜检查。当单独表达时，PF-8仅在细胞核中观察到，而Pol-8仅在细胞质中发现。然而，当共表达时，Pol-8与PF-8共易位到细胞核中。突变分析表明，PF-8含有核定位信号（NLS）以及位于N-末端和C-近端区域的结构域，这是Pol-8结合所需的。这项研究表明，使PF-8运输Pol-8进入细胞核的机制是Pol-8和PF-8在KSHV DNA合成中起作用的第一个关键步骤。(c)2005年爱思唯尔公司All rights reserved.
Kaposi's sarcoma-associated human herpesvirus (KSHV) encodes a processivity factor (PF-8, ORF59) that forms homodimers and binds to viral DNA polymerase (Pol-8, ORF9). PF-8 is essential for stabilizing Pol-8 on template DNA so that Pol-8 can incorporate nucleotides continuously. Here, the intracellular interaction of these two viral proteins was examined by confocal immunofluorescence microscopy. When individually expressed, PF-8 was observed exclusively in the nucleus, whereas Pol-8 was found only in the cytoplasm. However, when co-expressed, Pol-8 was co-translocated with PF-8 into the nucleus. Mutational analysis revealed that PF-8 contains a nuclear localization signal (NLS) as well as domains located at the N-terminus and the C-proximal regions that are required for Pol-8 binding. This study suggests that the mechanism that enables PF-8 to transport Pol-8 into the nucleus is the first critical step required for Pol-8 and PF-8 to function processively in KSHV DNA synthesis. (c) 2005 Elsevier Inc. All rights reserved.