Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins.

Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins.
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DOI:
10.1016/j.virol.2009.06.051
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发表时间:
2009-09-15
期刊:
影响因子:
3.7
通讯作者:
Morrison, Lynda A.
Morrison, Lynda A.
中科院分区:
医学3区
文献类型:
--
作者:
Cano-Monreal, Gina L.;Wylie, Kristine M.;Cao, Feng;Tavis, John E.;Morrison, Lynda A.

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疱疹病毒必须穿过内核膜和下面的核纤层才能离开细胞核。HSV-1 US 3和PKC可使核纤层蛋白磷酸化并诱导其分散,但不会引起感染期间产生的所有磷酸化核纤层蛋白种类。UL 13是在许多疱疹病毒中保守的丝氨酸苏氨酸蛋白激酶。HSV-1 UL 13磷酸化US 3,从而控制UL 31和UL 34核边缘定位,表明在核出口中的作用。在这里,我们报告说,单纯疱疹病毒-2 UL 13诱导核纤层蛋白A和C的构象变化和重新分配核纤层蛋白B1从核边缘到核内颗粒结构。HSV-2 UL 13在体外直接磷酸化核纤层蛋白A、C和B1,以及核纤层蛋白A1尾部结构域。HSV-2感染重现了单独表达UL 13时观察到的核纤层蛋白改变,并且还观察到其他改变,表明在HSV-2感染期间,另外的病毒和/或细胞蛋白与UL 13合作改变核纤层蛋白以允许核排出。
Herpesviruses must cross the inner nuclear membrane and underlying lamina to exit the nucleus. HSV-1 US3 and PKC can phosphorylate lamins and induce their dispersion but do not elicit all of the phosphorylated lamin species produced during infection. UL13 is a serine threonine protein kinase conserved among many herpesviruses. HSV-1 UL13 phosphorylates US3 and thereby controls UL31 and UL34 nuclear rim localization, indicating a role in nuclear egress. Here, we report that HSV-2 UL13 alone induced conformational changes in lamins A and C and redistributed lamin B1 from the nuclear rim to intranuclear granular structures. HSV-2 UL13 directly phosphorylated lamins A, C, and B1 in vitro, and the lamin A1 tail domain. HSV-2 infection recapitulated the lamin alterations seen upon expression of UL13 alone, and other alterations were also observed, indicating that additional viral and/or cellular proteins cooperate with UL13 to alter lamins during HSV-2 infection to allow nuclear egress.
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