Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cell Host Microbe. 2011 Nov 17;10(5):515-26. doi: 10.1016/j.chom.2011.09.012.
Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) and frequently also harbors Epstein-Barr virus (EBV). The expression of KSHV- and EBV-encoded microRNAs (miRNAs) in PELs suggests a role for these miRNAs in latency and lymphomagenesis. Using PAR-CLIP, a technology which allows the direct and transcriptome-wide identification of miRNA targets, we delineate the target sites for all viral and cellular miRNAs expressed in PEL cell lines. The resulting data set revealed that KSHV miRNAs directly target more than 2000 cellular mRNAs, including many involved in pathways relevant to KSHV pathogenesis. Moreover, 58% of these mRNAs are also targeted by EBV miRNAs, via distinct binding sites. In addition to a known viral analog of cellular miR-155, we show that KSHV encodes a viral miRNA that mimics cellular miR-142-3p function. In summary, this study identifies an extensive list of KSHV miRNA targets, which are likely to influence viral replication and pathogenesis.
原发性渗出性淋巴瘤（PEL）是由卡波西肉瘤相关疱疹病毒（KSHV）引起的，通常也含有 EBV。在 PEL 中表达的 KSHV 和 EBV 编码的 microRNAs（miRNAs）表明这些 miRNAs 在潜伏期和淋巴瘤发生中起作用。使用 PAR-CLIP，一种可以直接和转录组范围识别 miRNA 靶标的技术，我们描绘了在 PEL 细胞系中表达的所有病毒和细胞 miRNA 的靶标位点。由此产生的数据集表明，KSHV miRNAs 直接靶向超过 2000 个细胞 mRNA，包括许多与 KSHV 发病机制相关的途径中的 mRNA。此外，这些 mRNA 中有 58%也通过独特的结合位点被 EBV miRNAs 靶向。除了已知的细胞 miR-155 的病毒类似物外，我们还表明 KSHV 编码一种模拟细胞 miR-142-3p 功能的病毒 miRNA。总之，本研究确定了广泛的 KSHV miRNA 靶标列表，这些靶标可能影响病毒复制和发病机制。
