The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members
The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members
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DOI：
10.1016/j.virol.2003.10.019
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发表时间：
2004-02-20
期刊：
影响因子：
3.7
通讯作者：
Roller, RJ
中科院分区：
文献类型：
--
作者：
Ogg, PD;McDonell, PJ;Roller, RJ
由 1 型单纯疱疹病毒 (HSV-1) 编码的 Us3 蛋白激酶可抑制受感染细胞的细胞凋亡，并且足以阻止由 Bad 过度表达诱导的细胞凋亡 [Proc.国家。阿卡德。科学。 98（2001）10410]。虽然Us3可以诱导Bad的磷酸化，但Bad的磷酸化对于Us3的抗凋亡功能来说是可有可无的[J.病毒。 77（2003）6567]。我们用 Bad 扩展了这一发现，证明 Us3 可以阻断 Bid（凋亡途径中与 Bad 平行的因子）和 Bax（凋亡途径中 Bad 下游的因子）过表达诱导的细胞凋亡。之前的一份报告表明，Us3 在线粒体前阶段发挥作用 [J.病毒。 75 (2001) 549 1]，但我们的结果表明 Us3 在线粒体下游发挥抗凋亡作用。我们表明，Us3 的激酶活性对于 Us3 抗凋亡作用是必需的，因为催化失活形式的 Us3 无法阻止细胞凋亡。 Us3 的第二个功能，即病毒排出过程中的主要包膜，在伪狂犬病病毒 (PRV) 的 Us3 同源物中是保守的 [J.维罗尔将军。 82（2001）2363]。这里发表的实验表明，PRV Us3 还可以阻止 Bax 诱导的细胞凋亡，这表明 Us3 的抗细胞凋亡活性在 α-疱疹病毒中是保守的。 (C) 2004 Elsevier Inc. 保留所有权利。
The Us3 protein kinase encoded by herpes simplex virus type-1 (HSV-1) suppresses apoptosis in infected cells and is sufficient to block apoptosis induced by overexpression of Bad [Proc. Natl. Acad. Sci. 98 (2001) 10410]. While Us3 can induce phosphorylation of Bad, phosphorylation of Bad is dispensable for Us3 anti-apoptotic function [J. Virol. 77 (2003) 6567]. We extend the findings with Bad to demonstrate that Us3 blocks apoptosis induced by overexpression of Bid, a factor parallel to Bad in the apoptotic pathway, and Bax, a factor downstream of Bad in the apoptotic pathway. A previous report suggested that Us3 exerts its effects at a premitochondrial stage [J. Virol. 75 (2001) 549 1], but our results suggest that Us3 exerts anti-apoptotic effects downstream of the mitochondria. We show that the kinase activity of Us3 is necessary for Us3 anti-apoptotic effects, because a catalytically inactive form of Us3 was unable to block apoptosis. A second function of Us3, primary envelopment during viral egress, is conserved in the Us3 homologue of Pseudorabies virus (PRV) [J. Gen. Virol. 82 (2001) 2363]. Experiments published here demonstrate that PRV Us3 can also block apoptosis induced by Bax, suggesting that the antiapoptotic activity of Us3 is conserved across alpha-herpesviruses. (C) 2004 Elsevier Inc. All rights reserved.