Caspase 3 activation during herpes simplex virus 1 infection
Caspase 3 activation during herpes simplex virus 1 infection
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DOI：
10.1016/j.virusres.2006.03.003
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发表时间：
2006-09-01
期刊：
影响因子：
5
通讯作者：
Blaho, John A.
中科院分区：
文献类型：
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作者：
Kraft, Rachel M.;Nguyen, Marie L.;Blaho, John A.
在单纯疱疹病毒1型（HSV-1）感染期间，细胞凋亡由立即早期基因转录启动，随后由感染细胞中合成的蛋白质调节。我们以前已经表明，在HSV-1复制过程中，半胱氨酸天冬氨酸蛋白酶3的水平降低。我们现在证明，复制缺陷型HSV-1重组病毒，这是不能包装病毒DNA到衣壳激活半胱天冬酶3，但保留的能力，以防止细胞凋亡过程中杀死感染的细胞。这意味着HSV-1依赖性细胞凋亡不仅仅是对流产感染的反应。caspase 3活性形式的最大积累伴随着完全的HSV-1依赖性凋亡。此外，caspase 7被发现在HSV-1依赖性细胞凋亡过程中被激活。异位表达半胱天冬酶3的感染MCF-7细胞比其半胱天冬酶3无效的亲本细胞发生更有效的凋亡，证实半胱天冬酶3有助于HSV-1依赖性凋亡。然而，半胱天冬酶3重建没有使MCF-7细胞作为敏感的HEp-2细胞HSV-1依赖性凋亡，这表明其他细胞因子可能参与赋予抵抗这一进程。这些结果表明，半胱天冬酶3激活是HSV-1感染的结果，并在我们理解的病毒与宿主细胞的相互作用有重要意义。(c)2006 Elsevier B. V.保留所有权利。
During herpes simplex virus 1 (HSV-1) infection, apoptosis is initiated by immediate early gene transcription and is later modulated by proteins synthesized in infected cells. We have previously shown that procaspase 3 levels are reduced during HSV-1 replication. We now demonstrate that a replication-defective HSV-1 recombinant virus which is incapable of packaging viral DNA into capsids activated caspase 3 but retained the ability to prevent the apoptotic process from killing the infected cells. This implies that HSV-1-dependent apoptosis is not merely a response to abortive infection. Maximum accumulation of the active form of caspase 3 accompanied complete HSV-1-dependent apoptosis. Additionally, caspase 7 was found to be activated during HSV-1-dependent apoptosis. Infected MCF-7 cells which ectopically express caspase 3 underwent more efficient apoptosis than their caspase 3-null parental counterparts, confirming that caspase 3 contributes to HSV-1-dependent apoptosis. However, caspase 3 reconstitution did not make the MCF-7 cells as sensitive as HEp-2 cells to HSV-1-dependent apoptosis, suggesting that other cellular factors may be involved in conferring resistance to this process. These results indicate that caspase 3 activation is a consequence of HSV-1 infection and have important implications in our understanding of the interactions of the virus with host cells. (c) 2006 Elsevier B.V. All rights reserved.