Dynamin2 S-nitrosylation regulates adenovirus type 5 infection of epithelial cells.
Dynamin2 S-nitrosylation regulates adenovirus type 5 infection of epithelial cells.
复制标题
Dynamin2 S-亚硝基化调节上皮细胞的 5 型腺病毒感染。
DOI：
10.1099/vir.0.042713-0
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Daaka,Yehia
中科院分区：
文献类型：
--
作者：
Wang,Zhimin;Kim,JaeIl;Frilot,Nicole;Daaka,Yehia
动力蛋白2是调节囊泡运输的大的GT3，并且动力蛋白2的GT3活性是腺病毒感染的多步骤过程所需的。动力蛋白2的活性可能受到翻译后磷酸化和S-亚硝基化修饰的调节。在这项研究中，我们证明了dynamin 2S-亚硝基化在腺病毒感染上皮细胞中的作用。我们发现，腺病毒血清型5（Ad 5）感染增加了上皮细胞中一氧化氮（NO）的产生，并导致动力蛋白2的S-亚硝基化，主要是在半胱氨酸86（C86）和607（C607）残基上。携带C86 A和/或C607 A突变的动力蛋白2的强制过表达降低了Ad 5感染。通过RNAi诱导的内源性内皮NO合酶（eNOS）表达的敲低来减少NO合成，从而减弱病毒对靶细胞的感染。Ad 5感染促进动力蛋白2和eNOS的动力学动态S-亚硝基化：eNOS-亚硝基化迅速减少，动力蛋白2S-亚硝基化伴随增加。这些结果支持的假设，dynamin 2S-亚硝基化eNOS激活后促进腺病毒感染宿主上皮细胞。
Dynamin2 is a large GTPase that regulates vesicle trafficking, and the GTPase activity of dynamin2 is required for the multistep process of adenovirus infection. Activity of dynamin2 may be regulated by post-translational phosphorylation andS-nitrosylation modifications. In this study, we demonstrate a role for dynamin2S-nitrosylation in adenovirus infection of epithelial cells. We show that adenovirus serotype 5 (Ad5) infection augments production of nitric oxide (NO) in epithelial cells and causes theS-nitrosylation of dynamin2, mainly on cysteine 86 (C86) and 607 (C607) residues. Forced overexpression of dynamin2 bearing C86A and/or C607A mutations decreases Ad5 infection. Diminishing NO synthesis by RNAi-induced knockdown of endogenous endothelial NO synthase (eNOS) expression attenuates virus infection of target cells. Ad5 infection promotes the kinetically dynamicS-nitrosylation of dynamin2 and eNOS: there is a rapid decrease in eNOSS-nitrosylation and a concomitant increase in the dynamin2S-nitrosylation. These results support the hypothesis that dynamin2S-nitrosylation following eNOS activation facilitates adenovirus infection of host epithelial cells.