RIG-I 通过一种不依赖 RNA 聚合酶 III 的方式检测卡波氏肉瘤相关疱疹病毒的转录本。
RIG-I Detects Kaposi's Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner.
机构信息
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
出版信息
mBio. 2018 Jul 3;9(4):e00823-18. doi: 10.1128/mBio.00823-18.
Retinoic acid-inducible gene I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the innate immune response against many RNA viruses. We previously showed that RIG-I restricts Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation (J. A. West et al., J Virol 88:5778-5787, 2014, https://doi.org/10.1128/JVI.03226-13). In this study, we report that KSHV stimulates the RIG-I signaling pathway in a RNA polymerase (Pol) III-independent manner and subsequently induces type I interferon (IFN) responses. Knockdown or inhibition of RNA Pol III had no effect on beta interferon (IFN-β) induction by KSHV. By using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) approach, we identified multiple KSHV regions that give rise to RNA fragments binding to RIG-I, such as ORF8, Repeat region (LIR1), and ORF25 The sequence dissimilarity between these fragments suggests that RIG-I detects a particular structure rather than a specific sequence motif. Synthesized ORF8 RNA stimulated RIG-I-dependent but RNA Pol III-independent IFN-β signaling. In summary, several KSHV RNAs are sensed by RIG-I in a RNA Pol III-independent manner. Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Innate immune responses against viral infections, especially the induction of type I interferon, are critical for limiting the replication of viruses. Retinoic acid-inducible gene I (RIG-I), a cytosolic RNA helicase sensor, plays a significant role in the induction of type I interferon responses following viral infection. Here, we identified multiple RNA regions in KSHV as potential virus ligands that bind to RIG-I and stimulate RIG-I-dependent but RNA Pol III-independent IFN-β signaling. Our results expand the role of RIG-I by providing an example of a DNA virus activating a canonical RNA-sensing pathway.
视黄酸诱导基因 I（RIG-I）是一种胞质病原体识别受体，可引发针对多种 RNA 病毒的先天免疫反应。我们之前曾表明，RIG-I 限制卡波济肉瘤相关疱疹病毒（KSHV）的重新激活（J. A. West 等人，J Virol 88:5778-5787，2014 年，https://doi.org/10.1128/JVI.03226-13）。在这项研究中，我们报告说，KSHV 以 RNA 聚合酶（Pol）III 非依赖性方式刺激 RIG-I 信号通路，随后诱导 I 型干扰素（IFN）反应。RNA Pol III 的敲低或抑制对 KSHV 诱导β干扰素（IFN-β）没有影响。通过使用交联免疫沉淀（CLIP）方法分离的 RNA 的高通量测序（HITS-CLIP）方法，我们鉴定了多个 KSHV 区域，这些区域产生与 RIG-I 结合的 RNA 片段，例如 ORF8、重复区域（LIR1）和 ORF25。这些片段之间的序列差异表明 RIG-I 检测到特定结构而不是特定序列基序。合成的 ORF8 RNA 刺激 RIG-I 依赖性但 RNA Pol III 非依赖性 IFN-β 信号转导。总之，几种 KSHV RNA 以 RNA Pol III 非依赖性方式被 RIG-I 识别。卡波济肉瘤相关疱疹病毒（KSHV）是卡波济肉瘤、原发性渗出性淋巴瘤和多中心卡斯特曼病的病原体。针对病毒感染的先天免疫反应，特别是 I 型干扰素的诱导，对于限制病毒的复制至关重要。视黄酸诱导基因 I（RIG-I）是一种胞质 RNA 解旋酶传感器，在病毒感染后诱导 I 型干扰素反应中起重要作用。在这里，我们确定了 KSHV 中的多个 RNA 区域作为潜在的病毒配体，与 RIG-I 结合并刺激 RIG-I 依赖性但 RNA Pol III 非依赖性 IFN-β 信号转导。我们的结果通过提供一个 DNA 病毒激活经典 RNA 感应途径的例子，扩展了 RIG-I 的作用。
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