Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-Infected cells in a manner dependent on both UL34 and US3
Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-Infected cells in a manner dependent on both UL34 and US3
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DOI：
10.1128/jvi.00196-07
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发表时间：
2007-10-01
影响因子：
5.4
通讯作者：
Roller, Richard J.
中科院分区：
文献类型：
--
作者：
Leach, Natalie;Bjerke, Susan L.;Roller, Richard J.
用野生型单纯疱疹病毒1型（HSV-1）感染的细胞显示核膜下的核纤层组织的破坏。这种破坏反映在核纤层蛋白的定位和磷酸化的变化中。在这里，我们表明，HSV-1感染导致的LEM结构域蛋白emerin的重新定位。在用野生型病毒感染的细胞中，Emerin在核膜中变得更加移动的，并且在用不能表达UL 34蛋白（pUL 34）和US 3蛋白（pUS 3）的病毒感染的细胞中，Emerin不再与核纤层蛋白共定位，这表明感染导致Emerin和核纤层之间的连接丧失。感染以依赖于pUL 34和pUS 3的方式引起emerin的过度磷酸化。蛋白激酶C δ（PKC δ）抑制剂rottlerin可以抑制某些emerin的过度磷酸化。Emerin和pUL 34物理相互作用，如下拉和免疫共沉淀测定所示。然而，Emerin表达不是感染所必需的，因为病毒生长在来自Emerin缺失转基因小鼠的细胞中不受损害。结果表明，pUS 3和PKC δ已被pUL 34过度磷酸化emerin，导致其与核纤层蛋白的连接中断，并有助于核纤层的中断的模型。野生型HSV-1感染细胞的Emerin定位、核形状和核纤层蛋白组织特征的变化也发生在不产生病毒衣壳的重组病毒感染的细胞中，这表明这些变化的发生独立于衣壳蛋白。
Cells infected with wild-type herpes simplex virus type 1 (HSV-1) show disruption of the organization of the nuclear lamina that underlies the nuclear envelope. This disruption is reflected in changes in the localization and phosphorylation of lamin proteins. Here, we show that HSV-1 infection causes relocalization of the LEM domain protein emerin. In cells infected with wild-type virus, emerin becomes more mobile in the nuclear membrane, and in cells infected with viruses that fail to express UL34 protein (pUL34) and US3 protein (pUS3), emerin no longer colocalizes with lamins, suggesting that infection causes a loss of connection between emerin and the lamina. Infection causes hyperphosphorylation of emerin in a manner dependent upon both pUL34 and pUS3. Some emerin hyperphosphorylation can be inhibited by the protein kinase C delta (PKC delta) inhibitor rottlerin. Emerin and pUL34 interact physically, as shown by pull-down and coimmunoprecipitation assays. Emerin expression is not, however, necessary for infection, since virus growth is not impaired in cells derived from emerin-null transgenic mice. The results suggest a model in which pUS3 and PKC delta that has been recruited by pUL34 hyperphosphorylate emerin, leading to disruption of its connections with lamin proteins and contributing to the disruption of the nuclear lamina. Changes in emerin localization, nuclear shape, and lamin organization characteristic of cells infected with wild-type HSV-1 also occur in cells infected with recombinant virus that does not make viral capsids, suggesting that these changes occur independently of capsid envelopment.