HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS Pathog. 2013;9(9):e1003584. doi: 10.1371/journal.ppat.1003584. Epub 2013 Sep 5.
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.
卡波济肉瘤（KS）是由卡波济肉瘤相关疱疹病毒（KSHV）感染引起的。该病毒表达独特的 microRNAs（miRNAs），但其 miRNA 的靶点和功能尚不完全清楚。为了鉴定病毒 miRNA 的人类靶标，我们使用脉冲稳定同位素标记的氨基酸在细胞培养物（pSILAC）中测量了多种 KSHV miRNA 引起的蛋白质表达变化，在原代内皮细胞中进行。这导致了多个人类基因的鉴定，这些基因在蛋白质水平上受到抑制，但在 miRNA 水平上不受抑制。进一步的分析还表明，KSHV miRNA 可以调节上游调节因子的活性或表达，从而抑制脂磷酰丝氨酸处理后白细胞募集蛋白（ICAM1）的激活，上调促血管生成蛋白（HIF1α）和上调参与刺激血管生成的蛋白（HMOX1）。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。
