Accumulation of oxidized proteins in Herpesvirus infected cells.
Accumulation of oxidized proteins in Herpesvirus infected cells.
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DOI：
10.1016/j.freeradbiomed.2010.04.026
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发表时间：
2010-08-01
影响因子：
7.4
通讯作者：
Burch, April D.
中科院分区：
文献类型：
--
作者：
Mathew, Shomita S.;Bryant, Patrick W.;Burch, April D.
氧化应激产生了一种对蛋白质、脂质和DNA具有高度破坏性的环境。先前的研究表明，疱疹病毒感染引起细胞和组织中的氧化应激。病毒诱导的氧化应激的生物学后果尚未得到表征。许多研究小组的研究表明，通过氧化失衡受损的蛋白质要么被20 S蛋白酶体以不依赖于泛素的方式降解，要么形成对蛋白水解有抗性的聚集体。我们以前已经表明，单纯疱疹病毒1型（HSV-1）的复制显着增强的存在下，细胞的抗氧化剂分子伴侣热休克蛋白27，这表明这种蛋白质在管理病毒诱导的氧化应激可能的作用。在这里，我们表明，氧化蛋白积累在感染过程中与两个遥远的相关疱疹病毒，HSV-1和恒河猴Rhadinovirus（RRV），卡波西肉瘤相关疱疹病毒（KSHV）的近亲。氧化蛋白的存在并不完全出乎意料，因为之前已经记录了疱疹病毒感染期间的氧化应激。出乎意料的是，一些氧化的蛋白质在整个感染过程中以蛋白酶体依赖的方式被去除，而其他蛋白质则抵抗降解。抗蛋白水解的氧化蛋白被隔离在细胞核内的病灶中，并且与病毒诱导的伴侣蛋白富集结构域（VICE）（蛋白质质量控制的活性中心）无关，而是与我们实验室先前描述的Hsp 27富集病灶一致。实验还表明，氧化蛋白的积累在耗尽Hsp 27的细胞中更明显。我们建议，热休克蛋白27可以促进氧化蛋白质周转VICE结构域在核感染过程中。热休克蛋白27也可以缓冲毒性作用的高度羰基化，有缺陷的蛋白质，抵抗蛋白水解，促进其聚集在细胞核中。Hsp 27在病毒感染过程中的这些作用很可能不是相互排斥的。
Oxidative stress gives rise to an environment that can be highly damaging to proteins, lipids, and DNA. Previous studies indicate that Herpesvirus infections cause oxidative stress in cells and in tissues. The biological consequences of virus-induced oxidative stress have not been characterized. Studies from many groups indicate that proteins which have been damaged through oxidative imbalances are either degraded by the 20S proteasome in a ubiquitin-independent fashion or form aggregates that are resistant to proteolysis. We have previously shown that herpes simplex virus type 1 (HSV-1) replication was significantly enhanced in the presence of the cellular antioxidant chaperone Hsp27, indicating a possible role for this protein in managing virus-induced oxidative stress. Here we show that oxidized proteins accumulate during infections with two distantly related herpesviruses, HSV-1 and Rhesus Rhadinovirus (RRV), a close relative of the Kaposi’s sarcoma-associated herpesvirus (KSHV). The presence of oxidized proteins was not entirely unexpected as oxidative stress during herpesvirus infection has been previously documented. Unexpectedly, some oxidized proteins are removed in a proteasome-dependent fashion throughout infection and others resist degradation. Oxidized proteins that resist proteolysis become sequestered in foci within the nucleus and are not associated with virus-induced chaperone enriched domains (VICE), active centers of protein quality control, but rather coincide with Hsp27-enriched foci that were previously described by our laboratory. Experiments also indicate that the accumulation of oxidized proteins is more pronounced in cells depleted for Hsp27. We propose that Hsp27 may facilitate oxidized protein turnover at VICE domains in the nucleus during infection. Hsp27 may also buffer toxic effects of highly-carbonylated, defective proteins that resist proteolysis by promoting their aggregation in the nucleus. These roles of Hsp27 during virus infection are most likely not mutually exclusive.
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影响因子：
5.4
作者：
Burch, AD;Weller, SK
通讯作者：
Weller, SK
影响因子：
11.4
作者：
Ballesteros, M;Fredriksson, Å;Nyström, T
通讯作者：
Nyström, T
影响因子：
4.3
作者：
Lassoued, Saloua;Ben Ameur, Randa;Attia, Hammadi
通讯作者：
Attia, Hammadi
DOI：
10.3109/10715768609051640
发表时间：
1986-01-01
期刊：
Free radical research communications
影响因子：
--
作者：
Bannister, W H;Federici, G;Bannister, J V
通讯作者：
Bannister, J V
影响因子：
4.8
作者：
GRUNE, T;REINHECKEL, T;DAVIES, KJA
通讯作者：
DAVIES, KJA