Cano-Monreal Gina L, Wylie Kristine M, Cao Feng, Tavis John E, Morrison Lynda A
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 South Grand Blvd., St. Louis, MO 63104, USA.
Virology. 2009 Sep 15;392(1):137-47. doi: 10.1016/j.virol.2009.06.051. Epub 2009 Jul 28.
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.
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。单纯疱疹病毒1型（HSV-1）的US3和蛋白激酶C（PKC）可使核纤层蛋白磷酸化并诱导其分散，但不会引发感染期间产生的所有磷酸化核纤层蛋白种类。UL13是一种在许多疱疹病毒中保守的丝氨酸苏氨酸蛋白激酶。HSV-1的UL13使US3磷酸化，从而控制UL31和UL34在核膜边缘的定位，表明其在核出芽过程中发挥作用。在此，我们报告单纯疱疹病毒2型（HSV-2）的UL13单独就能诱导核纤层蛋白A和C发生构象变化，并使核纤层蛋白B1从核膜边缘重新分布到核内颗粒结构中。HSV-2的UL13在体外能直接使核纤层蛋白A、C和B1以及核纤层蛋白A1的尾部结构域磷酸化。HSV-2感染重现了单独表达UL13时所见到的核纤层蛋白改变，并且还观察到了其他改变，这表明在HSV-2感染期间，其他病毒和/或细胞蛋白与UL13协同作用来改变核纤层蛋白，以实现核出芽。
