C-terminal trans-activation sub-region of VP16 is uniquely required for forskolin-induced herpes simplex virus type 1 reactivation from quiescently infected-PC12 cells but not for replication in neuronally differentiated-PC12 cells.
C-terminal trans-activation sub-region of VP16 is uniquely required for forskolin-induced herpes simplex virus type 1 reactivation from quiescently infected-PC12 cells but not for replication in neuronally differentiated-PC12 cells.
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DOI：
10.1007/s13365-012-0137-7
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发表时间：
2013-02
影响因子：
3.2
通讯作者：
Miller, Craig S.
中科院分区：
文献类型：
--
作者：
Danaher, Robert J.;Cook, Ross K.;Wang, Chunmei;Triezenberg, Steven J.;Jacob, Robert J.;Miller, Craig S.
HSV-1被膜蛋白VP16含有一个反式激活结构域（TAD），该结构域是在裂解性感染和诱导潜伏期再激活时诱导立即早期（IE）基因所必需的。本研究报告了神经元和非神经元细胞中TAD的两个亚区在IE基因表达激活、病毒复制和静止感染(QIF)-PC12细胞再激活过程中的差异贡献。我们的研究表明，VP16-和化学（六亚甲基双乙酰胺）诱导的IE基因激活在神经元细胞中减弱。无论在神经元或非神经元细胞背景下，IE基因激活对VP16 TAD n端亚区（VP16N）的要求大于c端亚区（VP16C）。与这些发现相反，含有VP16N缺失的重组病毒（RP4）能够适度地诱导福斯克林诱导的再激活，而含有VP16C缺失的重组病毒（RP3）则不能诱导应激诱导的QIF-PC12细胞的再激活。VP16 TAD亚区这些独特的过程依赖功能在病毒生命周期的特定阶段（裂解、进入和维持静止状态以及再激活）可能很重要，因为病毒DNA可能会被不同程度地修饰。
The HSV-1 tegument protein VP16 contains a trans-activation domain (TAD) that is required for induction of immediate early (IE) genes during lytic infection and induced reactivation from latency. Here we report the differential contributions of the two sub-regions of the TAD in neuronal and non-neuronal cells during activation of IE gene expression, virus replication and reactivation from quiescently infected (QIF)-PC12 cells. Our studies show that VP16- and chemical (hexamethylenebisacetamide)-induced IE gene activation is attenuated in neuronal cells. Irrespective of neuronal or non-neuronal cell backgrounds, IE gene activation demonstrated a greater requirement for the N–terminal sub-region of VP16 TAD (VP16N) than the C-terminal sub-region (VP16C). In surprising contrast to these findings, a recombinant virus (RP4) containing the VP16N deletion was capable of modest forskolin-induced reactivation whereas a recombinant (RP3) containing a deletion of VP16C was incapable of stress-induced reactivation from QIF-PC12 cells. These unique process-dependent functions of the VP16 TAD sub-regions may be important during particular stages of the virus life cycle (lytic, entrance and maintenance of a quiescent state and reactivation) when viral DNA would be expected to be differentially modified.
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影响因子：
5.4
作者：
Cohrs, RJ;Randall, J;Tal-Singer, R
通讯作者：
Tal-Singer, R
影响因子：
3.2
作者：
Danaher, RJ;Jacob, RJ;Miller, CS
通讯作者：
Miller, CS
DOI：
10.1073/pnas.0400738101
发表时间：
2004-03-23
影响因子：
11.1
作者：
Eom, CY;Heo, WD;Lehman, IR
通讯作者：
Lehman, IR
影响因子：
3.2
作者：
Garrido, JJ;Carnicero, E;Schimmang, T
通讯作者：
Schimmang, T
影响因子：
5.4
作者：
Akhova, O;Bainbridge, M;Misra, V
通讯作者：
Misra, V