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Proteomic Screening of Human Targets of Viral microRNAs Reveals Functions Associated with Immune Evasion and Angiogenesis

机译:蛋白质组筛选的人类目标的病毒microRNAs揭示了与免疫逃逸和血管生成相关的功能。

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摘要

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.
机译:卡波西氏肉瘤(KS)是由卡波西氏肉瘤相关疱疹病毒(KSHV)感染引起的。该病毒表达独特的microRNA(miRNA),但这些miRNA的靶标和功能尚不完全清楚。为了鉴定病毒miRNA的人类靶标,我们在原代内皮细胞中使用细胞培养物中的氨基酸(pSILAC)进行脉冲稳定标记,测量了由多个KSHV miRNA引起的蛋白质表达变化。这导致鉴定了在蛋白质水平而不是在miRNA水平受抑制的多个人类基因。进一步的分析还确定,KSHV miRNA可以调节活性或上游调节因子的表达,导致溶血磷脂酸处理后参与白细胞募集的蛋白质(ICAM1)的活化受到抑制,以及促血管生成的蛋白质(HIF1α)上调),并上调与刺激血管生成有关的蛋白质(HMOX1)。这项研究有助于我们了解miRNA的抑制机制以及miRNA对病毒发病机制的贡献。

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