The US3 protein kinase blocks apoptosis induced by the d120 mutant of herpes simplex virus 1 at a premitochondrial stage
The US3 protein kinase blocks apoptosis induced by the d120 mutant of herpes simplex virus 1 at a premitochondrial stage
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DOI：
10.1128/jvi.75.12.5491-5497.2001
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发表时间：
2001-06-01
影响因子：
5.4
通讯作者：
Roizman, B
中科院分区：
文献类型：
--
作者：
Munger, J;Chee, AV;Roizman, B
早些时候d120突变体的研究表明,单纯疱疹病毒1,缺少alpha4基因的两个副本,诱发caspase-3-dependent HEp-2细胞凋亡,细胞凋亡也引起alpha4 rescuant但被rescuant互补的DNA片段编码U (S) 3蛋白激酶(R,源和B, Roizman Proc。国家的,学会科学,美国93:9583 - 9587,1996,和R .源,C,范桑特,和B, Roizman, Proc。国家的,学会科学,美国94:7891 - 7896,1997),为了研究其在凋亡级联中的作用，在人巨细胞病毒立即早期启动子的控制下，将U(S)3开放阅读框克隆到杆状病毒（Bac-U(S)3）中，我们报告了以下结果：(i) Bac-U(S)3阻断procaspase-3向活性caspase的加工，在d120突变体感染后3小时，如果与Bac-U(S)3重复感染，procaspase-3水平保持不变；但是在d120突变体感染后9小时，大量的procaspase-3仍然存在于被Bac-Us3重复感染的细胞中，（ii） U(S)3蛋白激酶阻断了线粒体参与的上游的促凋亡级联，因为Bac-U(S)3阻断了d120突变体感染的细胞中细胞色素c的释放，（iii）同时感染Sac-U(S)3和d120突变体的HEp-2细胞并没有改变ICP0， -22或-27的积累或加工模式。因此，U(S)3似乎不会通过靶向这些蛋白来阻止细胞凋亡。
Earlier studies have shown that the d120 mutant of herpes simplex virus 1, which lacks both copies of the alpha4 gene, induces caspase-3-dependent apoptosis in HEp-2 cells, Apoptosis was also induced by the alpha4 rescuant but was blocked by the complementation of rescuant with a DNA fragment encoding the U(S)3 protein kinase (R, Leopardi and B, Roizman, Proc. Natl, Acad. Sci, USA 93:9583-9587, 1996, and R. Leopardi, C, Van Sant, and B, Roizman, Proc. Natl, Acad. Sci, USA 94:7891-7896, 1997), To investigate its role in the apoptotic cascade, the U(S)3 open reading frame was cloned into a baculovirus (Bac-U(S)3) under the control of the human cytomegalovirus immediate-early promoter, We report the following, (i) Bac-U(S)3 blocks processing of procaspase-3 to active caspase, Procaspase-3 levels remained unaltered if superinfected with Bac-U(S)3 at 3 h after d120 mutant infection, but significant amounts of procaspase-3 remained in cells superinfected with Bac-Us3 at 9 h postinfection with d120 mutant, (ii) The U(S)3 protein kinase blocks the proapoptotic cascade upstream of mitochondrial involvement inasmuch as Bac-U(S)3 blocks release of cytochrome c in cells infected with the d120 mutant, (iii) Concurrent infection of HEp-2 cells with Sac-U(S)3 and the d120 mutant did not alter the pattern of accumulation or processing of ICP0, -22, or -27, acid therefore U(S)3 does not appear to block apoptosis by targeting these proteins.