Regulation of promyelocytic leukemia (PML) protein levels and cell morphology by bovine herpesvirus 1 infected cell protein 0 (bICP0) and mutant bICP0 proteins that do not localize to the nucleus
Regulation of promyelocytic leukemia (PML) protein levels and cell morphology by bovine herpesvirus 1 infected cell protein 0 (bICP0) and mutant bICP0 proteins that do not localize to the nucleus
复制标题
DOI：
10.1016/j.virusres.2010.12.010
复制
发表时间：
2011-03-01
期刊：
影响因子：
5
通讯作者：
Jones, Clinton
中科院分区：
文献类型：
--
作者：
Gaudreault, Natasha;Jones, Clinton
BHV-1是一种重要的牛病原。BHV-1编码的感染细胞蛋白0(BICP0)是一种重要的调节蛋白，因为它是结构性表达的，可以激活病毒的所有启动子。BICP0激活病毒启动子的机制还不是很清楚，因为bICP0似乎不是一个序列特异性结合蛋白。BICP0 N端的C3HC4锌环(真正有趣的新基因)基序具有E3泛素连接酶活性，对激活病毒基因表达和抑制干扰素依赖的转录具有重要作用。与其他阿尔法疱疹病毒ICPO同源物一样，bICP0与含有早幼粒细胞白血病(PML)蛋白的核区相关。在培养细胞的生产性感染过程中，BHV-1诱导PML蛋白的降解，这与有效的生产性感染有关。在这项研究中，我们证明了表达bICP0的质粒降低了PML蛋白的稳态水平，而C3HC4锌环指对PML的降解是重要的。令人惊讶的是，缺乏核定位信号的完整C3HC4锌环指的bICP0突变体也降低了稳定的PML蛋白水平。此外，突变的bICP0蛋白主要定位在细胞质中，诱导了转基因细胞的形态变化。在生产性感染过程中，在低传代牛肾的细胞质中检测到bICP0，但在已建立的牛肾细胞中未检测到bICP0。这些研究表明，即使bICP0不能有效地定位于细胞核，也能够诱导PML蛋白的降解，并改变转基因细胞的形态。(C)2010爱思唯尔B.V.保留所有权利。
BHV-1 is an important pathogen of cattle. The infected cell protein 0 (bICP0) encoded by BHV-1 is an important regulatory protein because it is constitutively expressed and can activate all viral promoters. The mechanism by which bICP0 activates viral promoters is not well understood because bICP0 does not appear to be a sequence specific binding protein. A C3HC4 zinc RING (really interesting novel gene) motif at the N-terminus of bICP0 has E3 ubiquitin ligase activity, which is important for activating viral gene expression and inhibiting interferon dependent transcription. Like other alpha-herpesvirinae ICPO homologues, bICP0 is associated with promyelocytic leukemia (PML) protein-containing nuclear domains. During productive infection of cultured cells, BHV-1 induces degradation of the PML protein, which correlates with efficient productive infection. In this study, we demonstrated that a plasmid expressing bICP0 reduces steady state levels of the PML protein, and the C3HC4 zinc RING finger is important for PML degradation. Surprisingly, bICP0 mutants with an intact C3HC4 zinc RING finger that lack a nuclear localization signal also reduces steady PML protein levels. In addition, mutant bICP0 proteins that primarily localize to the cytoplasm induced morphological changes in transfected cells. During productive infection, bICP0 was detected in the cytoplasm of low-passage bovine kidney, but not established bovine kidney cells. These studies demonstrated that bICP0, even when not able to efficiently localize to the nucleus, was able to induce degradation of the PML protein and alter the morphology of transfected cells. (C) 2010 Elsevier B.V. All rights reserved.