Proteomic screening of human targets of viral microRNAs reveals functions associated with immune evasion and angiogenesis.
Proteomic screening of human targets of viral microRNAs reveals functions associated with immune evasion and angiogenesis.
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DOI：
10.1371/journal.ppat.1003584
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Ziegelbauer J
中科院分区：
文献类型：
--
作者：
Gallaher AM;Das S;Xiao Z;Andresson T;Kieffer-Kwon P;Happel C;Ziegelbauer J
卡波西肉瘤（KS）是由卡波西肉瘤相关疱疹病毒（KSHV）感染引起的。该病毒表达独特的microRNA（miRNAs），但这些miRNAs的靶点和功能尚未完全了解。为了鉴定病毒miRNA的人类靶点，我们在原代内皮细胞中使用细胞培养物中氨基酸脉冲稳定标记（pSILAC）测量了由多种KSHV miRNA引起的蛋白质表达变化。这导致了在蛋白质水平上被抑制的多个人类基因的鉴定，而不是在miRNA水平上。进一步的分析还发现，KSHV miRNA可以调节上游调控因子的活性或表达，导致溶血磷脂酸处理后参与白细胞募集的蛋白（ICAM 1）的活化受到抑制，以及促血管生成蛋白（HIF 1 α）的上调和参与刺激血管生成的蛋白（HMOX 1）的上调。这项研究有助于我们理解miRNA的抑制机制和miRNA对病毒发病机制的贡献。卡波西肉瘤相关疱疹病毒是与多种增殖性疾病相关的病毒，包括卡波西肉瘤，原发性渗出性淋巴瘤和多中心Castleman病。这种病毒表达小核酸（具有与其他生物不同的序列），称为microRNA，可以限制特定基因的表达。目前，我们只知道这些病毒microRNA的几个有效靶点，microRNA介导的抑制机制仍在积极争论中。我们使用一种方法来观察这些病毒microRNA诱导的蛋白质表达变化，以更好地了解microRNA的靶点和功能。我们在这里描述的方法发现了其他方法错过的microRNA靶点。除了鉴定以前的microRNA靶点和发现新的microRNA靶点外，我们还发现特定病毒microRNA的功能与免疫逃避和血管网络扩张有关，这是卡波西肉瘤的标志。这些结果可能是研究其他生物体microRNA的资源，此外，所描述的microRNA功能为病毒发病机制和免疫逃避提供了机制见解。
Kaposi's sarcoma (KS) is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV). The virus expresses unique microRNAs (miRNAs), but the targets and functions of these miRNAs are not completely understood. In order to identify human targets of viral miRNAs, we measured protein expression changes caused by multiple KSHV miRNAs using pulsed stable labeling with amino acids in cell culture (pSILAC) in primary endothelial cells. This led to the identification of multiple human genes that are repressed at the protein level, but not at the miRNA level. Further analysis also identified that KSHV miRNAs can modulate activity or expression of upstream regulatory factors, resulting in suppressed activation of a protein involved in leukocyte recruitment (ICAM1) following lysophosphatidic acid treatment, as well as up-regulation of a pro-angiogenic protein (HIF1α), and up-regulation of a protein involved in stimulating angiogenesis (HMOX1). This study aids in our understanding of miRNA mechanisms of repression and miRNA contributions to viral pathogenesis. Kaposi's sarcoma-associated herpesvirus is the virus associated with multiple proliferative disorders, including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. This virus expresses small nucleic acids (with sequences distinct from other organisms), called microRNAs, that can limit expression of specific genes. Currently, we only know a few validated targets of these viral microRNAs and the mechanisms of microRNA-mediated repression are still being actively debated. We used a method to look at protein expression changes induced by these viral microRNAs to better understand microRNA targets and functions. The method we describe here found microRNA targets that are missed by other approaches. In addition to identifying previous microRNA targets and discovering new microRNA targets, we found the function of specific viral microRNAs to be associated with immune evasion and the expansion of blood vessel networks, a hallmark of Kaposi's sarcoma. The results may be a resource for those studying microRNAs from other organisms, and furthermore, the microRNA functions described provide mechanistic insight into viral pathogenesis and immune evasion.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
通过病毒发育开关激活宿主翻译控制途径。
影响因子：
6.7
作者：
Arias C;Walsh D;Harbell J;Wilson AC;Mohr I
通讯作者：
Mohr I
影响因子：
56.9
作者：
Kamura, T;Koepp, DM;Conway, JW
通讯作者：
Conway, JW
影响因子：
10.5
作者：
Hansen, Amy;Henderson, Stephen;Boshoff, Chris
通讯作者：
Boshoff, Chris
DOI：
10.1016/s1357-2725(02)00172-3
发表时间：
2003-03-01
影响因子：
4
作者：
Abdel-Aziz, MT;El-Asmar, MF;Kamal, N
通讯作者：
Kamal, N